Growth differentiation factor 15: A novel biomarker with high clinical potential

References

• Bootcov MR, Bauskin AR, Valenzuela SM. MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-beta superfamily. Proc Natl Acad Sci USA. 1997;94:11514–11519.
   PubMed Web of Science ®Google Scholar
• Breit SN, Johnen H, Cook AD, et al. The TGF-β superfamily cytokine, MIC-1/GDF15: a pleotrophic cytokine with roles in inflammation, cancer and metabolism. Growth Factors. 2011;29:187–195.
   PubMed Web of Science ®Google Scholar
• Paralkar VM, Vail AL, Grasser WA, et al. Cloning and characterization of a novel member of the transforming growth factor-beta/bone morphogenetic protein family. J Biol Chem. 1998;273:13760–13767.
   PubMed Web of Science ®Google Scholar
• Böttner M, Suter-Crazzolara C, Schober A, et al. Expression of a novel member of the TGF-beta superfamily, growth/differentiation factor-15/macrophage-inhibiting cytokine-1 (GDF-15/MIC-1) in adult rat tissues. Cell Tissue Res. 1999;297:103–110.
   PubMed Web of Science ®Google Scholar
• Yokoyama-Kobayashi M, Saeki M, Sekine S, et al. Human cDNA encoding a novel TGF-beta superfamily protein highly expressed in placenta. J Biochem. 1997;122:622–626.
   PubMed Web of Science ®Google Scholar
• Lawton LN, Bonaldo MF, Jelenc PC, et al. Identification of a novel member of the TGF-beta superfamily highly expressed in human placenta. Gene. 1997;203:17–26.
   PubMed Web of Science ®Google Scholar
• Kempf T, Eden M, Strelau J, et al. The transforming growth factor-superfamily member growth-differentiation factor-15 protects the heart from ischemia/reperfusion injury. Circ Res. 2006;98:351–360.
   PubMed Web of Science ®Google Scholar
• Hsiao EC, Koniaris LG, Zimmers-Koniaris T, et al. Characterization of growth-differentiation factor 15, a transforming growth factor beta superfamily member induced following liver injury. Mol Cell Biol. 2000;20:3742–3751.
   PubMed Web of Science ®Google Scholar
• Kim KS, Baek SJ, Flake GP, et al. Expression and regulation of nonsteroidal anti-inflammatory drug-activated gene (NAG-1) in human and mouse tissue. Gastroenterology. 2002;122:1388–1398.
   PubMed Web of Science ®Google Scholar
• Li PX, Wong J, Ayed A, et al. Placental transforming growth factor-beta is a downstream mediator of the growth arrest and apoptotic response of tumor cells to DNA damage and p53 overexpression. J Biol Chem. 2000;275:20127–20135.
   PubMed Web of Science ®Google Scholar
• Hromas R, Hufford M, Sutton J, et al. PLAB, a novel placental bone morphogenetic protein. Biochim Biophys Acta. 1997;1354:40–44.
   PubMedGoogle Scholar
• Johnen H, Lin S, Kuffner T, et al. Tumor-induced anorexia and weight loss are mediated by the TGF-beta superfamily cytokine MIC-1. Nat Med. 2007;13:1333–1340.
   PubMed Web of Science ®Google Scholar
• Tsai VW, Macia L, Johnen H, et al. TGF-b superfamily cytokine MIC-1/GDF15 is a physiological appetite and body weight regulator. PLoS One. 2013;8:e55174.
   PubMed Web of Science ®Google Scholar
• Baek SJ, Okazaki R, Lee SH, et al. Nonsteroidal anti-inflammatory drug-activated gene-1 over expression in transgenic mice suppresses intestinal neoplasia. Gastroenterology. 2006;131:1553–1560.
   PubMed Web of Science ®Google Scholar
• Baek SJ, Kim JS, Moore SM, et al. Cyclooxygenase inhibitors induce the expression of the tumor suppressor gene EGR-1, which results in the up-regulation of NAG-1, an antitumorigenic protein. Mol Pharmacol. 2005;67:356–364.
   PubMed Web of Science ®Google Scholar
• Ünal B, Alan S, Başsorgun Cİ, et al. The divergent roles of growth differentiation factor-15 (GDF-15) in benign and malignant skin pathologies. Arch Dermatol Res. 2015;307:551.
   PubMed Web of Science ®Google Scholar
• Li C, Wang J, Kong J, et al. GDF15 promotes EMT and metastasis in colorectal cancer. Oncotarget. 2016;7:860–872.
   PubMedGoogle Scholar
• Li YL, Chang JT, Lee LY, et al. GDF15 contributes to radioresistance and cancer stemness of head and neck cancer by regulating cellular reactive oxygen species via a SMAD-associated signaling pathway. Oncotarget. 2017;8:1508–1528.
   PubMedGoogle Scholar
• Bauskin AR, Zhang HP, Fairlie WD, et al. The propeptide of macrophage inhibitory cytokine (MIC-1), a TGF-β superfamily member, acts as a quality control determinant for correctly folded MIC-1. Embo J. 2000;19:2212–2220.
   PubMed Web of Science ®Google Scholar
• Li JJ, Liu J, Lupino K, et al. Growth differentiation factor 15 maturation requires proteolytic cleavage by PCSK3, -5, and -6. Mol Cell Biol. 2018;38:pii: e00249-18. Print 2018 Nov 1.
   Web of Science ®Google Scholar
• Bauskin AR, Brown DA, Junankar S, et al. The propeptide mediates formation of stromal stores of PROMIC-1: role in determining prostate cancer outcome. Cancer Res. 2005;65:2330–2336.
   PubMed Web of Science ®Google Scholar
• Hsu JY, Crawley S, Chen M, et al. Non-homeostatic body weight regulation through a brainstem-restricted receptor for GDF15. Nature. 2017;550:255–259.
   PubMed Web of Science ®Google Scholar
• Yang L, Chang CC, Sun Z, et al. GFRAL is the receptor for GDF15 and is required for the anti-obesity effects of the ligand. Nat Med. 2017;23:1158–1166.
   PubMed Web of Science ®Google Scholar
• Mullican SE, Lin-Schmidt X, Chin CN, et al. GFRAL is the receptor for GDF15 and the ligand promotes weight loss in mice and nonhuman primates. Nat Med. 2017;23:1150–1157.
   PubMed Web of Science ®Google Scholar
• Emmerson PJ, Wang F, Du Y, et al. The metabolic effects of GDF15 are mediated by the orphan receptor GFRAL. Nat Med. 2017;23:1215–1219.
   PubMed Web of Science ®Google Scholar
• Schledzewski K, Géraud C, Arnold B, et al. Deficiency of liver sinusoidal scavenger receptors stabilin-1 and -2 in mice causes glomerulofibrotic nephropathy via impaired hepatic clearance of noxious blood factors. J Clin Invest. 2011;121:703–714.
   PubMed Web of Science ®Google Scholar
• Moore AG, Brown DA, Fairlie WD, et al. The transforming growth factor-ss superfamily cytokine macrophage inhibitory cytokine-1 is present in high concentrations in the serum of pregnant women. J Clin Endocrinol Metab. 2000;85:4781–4788.
   PubMed Web of Science ®Google Scholar
• Tong S, Marjono B, Brown DA, et al. Serum concentrations of macrophage inhibitory cytokine 1 (MIC 1) as a predictor of miscarriage. Lancet. 2004;363:129–130.
   PubMed Web of Science ®Google Scholar
• Wollert KC, Kempf T, Wallentin L. Growth differentiation factor 15 as a biomarker in cardiovascular disease. Clin Chem. 2017;63:140–151.
   PubMed Web of Science ®Google Scholar
• Corre J, Hébraud B, Bourin P. Concise review: growth differentiation factor 15 in pathology: a clinical role? Stem Cells Transl Med. 2013;2:946–952.
   PubMed Web of Science ®Google Scholar
• Mimeault M, Batra KS. Divergent molecular mechanisms underlying the pleiotropic functions of macrophage inhibitory cytokine-1. J Cell Physiol. 2010;224:626–635.
   PubMed Web of Science ®Google Scholar
• Jiang J, Thalamuthu A, Ho JE, et al. A meta-analysis of genome-wide association studies of growth differentiation factor-15 concentration in blood. Front Genet. 2018;9:97.
   PubMed Web of Science ®Google Scholar
• Khan SQ, Ng K, Dhillon O, et al. Growth differentiation factor-15 as a prognostic marker in patients with acute myocardial infarction. Eur Heart J. 2009;30:1057–1065.
   PubMed Web of Science ®Google Scholar
• Kempf T, Horn-Wichmann R, Brabant G, et al. Circulating concentrations of growth-differentiation factor 15 in apparently healthy elderly individuals and patients with chronic heart failure as assessed by a new immunoradiometric sandwich assay. Clin Chem. 2007;53:284–291.
   PubMed Web of Science ®Google Scholar
• Daniels LB, Clopton P, Laughlin GA, et al. Growth-differentiation factor-15 is a robust, independent predictor of 11-year mortality risk in community-dwelling older adults: the Rancho Bernardo Study. Circulation. 2011;123:2101–2110.
   PubMed Web of Science ®Google Scholar
• Kempf T, Guba-Quint A, Torgerson J, et al. Growth differentiation factor 15 predicts future insulin resistance and impaired glucose control in obese nondiabetic individuals: results from the XENDOS trial. Eur J Endocrinol. 2012;167:671–678.
   PubMed Web of Science ®Google Scholar
• Lancrajan I, Schneider-Stock R, Naschberger E, et al. Absolute quantification of DcR3 and GDF15 from human serum by LC-ESI MS. J Cell Mol Med. 2015;19:1656–1671.
   PubMed Web of Science ®Google Scholar
• Brown DA, Ward RL, Buckhaults P, et al. MIC-1 serum level and genotype: associations with progress and prognosis of colorectal carcinoma. Clin Cancer Res. 2003;9:2642–2650.
   PubMed Web of Science ®Google Scholar
• Ho JE, Mahajan A, Chen MH, et al. Clinical and genetic correlates of growth differentiation factor 15 in the community. Clin Chem. 2012;58:1582–1591.
   PubMed Web of Science ®Google Scholar
• Fejzo MS, Arzy D, Tian R, et al. Evidence GDF15 plays a role in familial and recurrent hyperemesis gravidarum. Geburtshilfe Frauenheilkd. 2018;78:866–870.
   PubMed Web of Science ®Google Scholar
• Hsu LA, Wu S, Juang JJ, et al. Growth differentiation factor 15 may predict mortality of peripheral and coronary artery diseases and correlate with their risk factors. Mediators Inflamm. 2017;2017:9398401.
   PubMed Web of Science ®Google Scholar
• Xiang Y, Zhang T, Guo J, et al. The association of growth differentiation factor-15 gene polymorphisms with growth differentiation factor-15 serum levels and risk of ischemic stroke. J Stroke Cerebrovasc Dis. 2017;26:2111–2119.
   PubMed Web of Science ®Google Scholar
• Wang X, Yang X, Sun K, et al. The haplotype of the growth-differentiation factor 15 gene is associated with left ventricular hypertrophy in human essential hypertension. Clin Sci. 2009;118:137–145.
   PubMed Web of Science ®Google Scholar
• Doerstling S, Hedberg P, Öhrvik J, et al. Growth differentiation factor 15 in a community-based sample: age-dependent reference limits and prognostic impact. Ups J Med Sci. 2018;123:86–93.
   PubMed Web of Science ®Google Scholar
• Tsai VW, Macia L, Feinle-Bisset C, et al. Serum levels of human MIC-1/GDF15 vary in a diurnal pattern, do not display a profile suggestive of a satiety factor and are related to BMI. PLoS One. 2015;10:e0133362.
   PubMed Web of Science ®Google Scholar
• Eggers KM, Kempf T, Wallentin L, et al. Change in growth differentiation factor 15 concentrations over time independently predicts mortality in community-dwelling elderly individuals. Clin Chem. 2013;59:1091–1098.
   PubMed Web of Science ®Google Scholar
• Rohatgi A, Patel P, Das SR, et al. Association of growth differentiation factor-15 with coronary atherosclerosis and mortality in a young, multiethnic population = observations from the Dallas Heart Study. Clin Chem. 2012;58:172–182.
   PubMed Web of Science ®Google Scholar
• Fluschnik N, Ojeda F, Zeller T, et al. Predictive value of long-term changes of growth differentiation factor-15 over a 27-year-period for heart failure and death due to coronary heart disease. PLoS One. 2018;13:e0197497.
   PubMed Web of Science ®Google Scholar
• Brown DA, Breit SN, Buring J, et al. Concentration in plasma of macrophage inhibitory cytokine-1 and risk of cardiovascular events in women: a nested case-control study. Lancet. 2002;359:2159–2163.
   PubMed Web of Science ®Google Scholar
• Wang TJ, Wollert KC, Larson MG, et al. Prognostic utility of novel biomarkers of cardiovascular stress: the Framingham Heart Study. Circulation. 2012;126:1596–1604.
   PubMed Web of Science ®Google Scholar
• Ho JE, Lyass A, Courchesne P, et al. Protein biomarkers of cardiovascular disease and mortality in the community. J Am Heart Assoc. 2018;7:e008108.
   PubMed Web of Science ®Google Scholar
• Wiklund FE, Bennet AM, Magnusson PK, et al. Macrophage inhibitory cytokine-1 (MIC-1/GDF15): a new marker of all-cause mortality. Aging Cell. 2010;9:1057–1064.
   PubMed Web of Science ®Google Scholar
• Wallentin L, Zethelius B, Berglund L, et al. GDF-15 for prognostication of cardiovascular and cancer morbidity and mortality in men. PLoS One. 2013;8:e78797.
   PubMed Web of Science ®Google Scholar
• Jiang J, Wen W, Brown DA, et al. The relationship of serum macrophage inhibitory cytokine-1 levels with gray matter volumes in community-dwelling older individuals. PLoS One. 2015;10:e0123399.
   PubMed Web of Science ®Google Scholar
• Kempf T, Zarbock A, Widera C, et al. GDF-15 is an inhibitor of leukocyte integrin activation required for survival after myocardial infarction in mice. Nat Med. 2011;17:581–588.
   PubMed Web of Science ®Google Scholar
• Yamashita H, Shimizu A, Kato M, et al. Growth/differentiation factor-5 induces angiogenesis in vivo. Exp Cell Res. 1997;235:218–226.
   PubMed Web of Science ®Google Scholar
• Frank D, Kuhn C, Brors B, et al. Gene expression pattern in biomechanically stretched cardiomyocytes: evidence for a stretch-specific gene program. Hypertension. 2008;51:309–318.
   PubMed Web of Science ®Google Scholar
• George M, Jena A, Srivatsan V, et al. GDF 15-a novel biomarker in the offing for heart failure. Curr Cardiol Rev. 2016;12:37–46.
   PubMed Web of Science ®Google Scholar
• Anand IS, Kempf T, Rector TS, et al. Serial measurement of growth-differentiation factor-15 in heart failure: relation to disease severity and prognosis in the Valsartan Heart Failure Trial. Circulation. 2010;122:1387–1395.
   PubMed Web of Science ®Google Scholar
• Kempf T, von Haehling S, Peter T, et al. Prognostic utility of growth differentiation factor-15 in patients with chronic heart failure. J Am Coll Cardiol. 2007;50:1054–1060.
   PubMed Web of Science ®Google Scholar
• Lok DJ, Klip IT, Lok SI, et al. Incremental prognostic power of novel biomarkers (growth-differentiation factor-15, high-sensitivity C-reactive protein, galectin-3, and high-sensitivity troponin-T) in patients with advanced chronic heart failure. Am J Cardiol. 2013;112:831–837.
   PubMed Web of Science ®Google Scholar
• Peeters J, Sanders-van Wijk S, Bektas S, et al. Biomarkers in outpatient heart failure management; are they correlated to and do they influence clinical judgment? Neth Heart J. 2014;22:115–121.
   PubMed Web of Science ®Google Scholar
• Gaggin HK, Szymonifka J, Bharadwaj A, et al. Head-to-head comparison of serial soluble ST2, growth differentiation factor 15, and highly-sensitive troponin T measurements in patients with chronic heart failure. J Am Coll Cardiol HF. 2014;2:65–72.
   Google Scholar
• Richter B, Koller L, Hohensinner PJ, et al. A multi-biomarker risk score improves prediction of long-term mortality in patients with advanced heart failure. Int J Cardiol. 2013;168:1251–1257.
   PubMed Web of Science ®Google Scholar
• Wang F, Guo Y, Yu H, et al. Growth differentiation factor 15 in different stages of heart failure: potential screening implications. Biomarkers. 2010;15:671–676.
   PubMed Web of Science ®Google Scholar
• Santhanakrishnan R, Chong JPC, Ng TP, et al. Growth differentiation factor 15, ST2, high-sensitivity troponin T, and N-terminal probrain natriuretic peptide in heart failure with preserved vs. reduced ejection fraction. Eur J Heart Fail. 2012;14:1338–1347.
   PubMed Web of Science ®Google Scholar
• Stahrenberg R, Edelmann F, Mende M, et al. The novel biomarker growth differentiation factor- 15 in heart failure with normal ejection fraction. Eur J Heart Fail. 2010;12:1309–1316.
   PubMed Web of Science ®Google Scholar
• Dinh W, Füth R, Lankisch M, et al. Growth-differentiation factor15: a novel biomarker in patients with diastolic dysfunction? Arq Bras Cardiol. 2011;97:65–75.
   PubMed Web of Science ®Google Scholar
• Izumiya Y, Hanatani S, Kimura Y, et al. Growth differentiation factor-15 is a useful prognostic marker in patients with heart failure with preserved ejection fraction. Can J Cardiol. 2014;30:338–344.
   PubMed Web of Science ®Google Scholar
• Manhenke C, Ørn S, von Haehling S, et al. Clustering of 37 circulating biomarkers by exploratory factor analysis in patients following complicated acute myocardial infarction. Int J Cardiol. 2013;166:729–735.
   PubMed Web of Science ®Google Scholar
• Dominguez-Rodriguez A, Abreu-Gonzalez P, Avanzas P. Relation of growth-differentiation factor 15 to left ventricular remodeling in ST-segment elevation myocardial infarction. Am J Cardiol. 2011;108:955–958.
   PubMed Web of Science ®Google Scholar
• Lin JF, Wu S, Hsu SY, et al. Growth-differentiation factor-15 and major cardiac events. Am J Med Sci. 2014;347:305–311.
   PubMed Web of Science ®Google Scholar
• Lind L, Wallentin L, Kempf T, et al. Growth-differentiation factor15 is an independent marker of cardiovascular dysfunction and disease in the elderly: results from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) Study. Eur Heart J. 2009;30:2346–2353.
   PubMed Web of Science ®Google Scholar
• Xanthakis V, Larson MG, Wollert KC, et al. Association of novel biomarkers of cardiovascular stress with left ventricular hypertrophy and dysfunction: implications for screening. J Am Heart Assoc. 2013;2:e000399.
   PubMed Web of Science ®Google Scholar
• Bonaca MP, Morrow DA, Braunwald E, et al. Growth differentiation factor-15 and risk of recurrent events in patients stabilized after acute coronary syndrome: observations from PROVE IT-TIMI 22. Arterioscler Thromb Vasc Biol. 2011;31:203–210.
   PubMed Web of Science ®Google Scholar
• Li J, Cui Y, Huang A, et al. Additional diagnostic value of growth differentiation factor-15 (GDF-15) to N-Terminal B-Type Natriuretic Peptide (NT-proBNP) in patients with different stages of heart failure. Med Sci Monit. 2018;24:4992–4999.
   PubMed Web of Science ®Google Scholar
• Wang FF, BX1 C, Yu HY, et al. Correlation between growth differentiation factor-15 and collagen metabolism indicators in patients with myocardial infarction and heart failure. J Geriatr Cardiol. 2016;13:88–93.
   PubMedGoogle Scholar
• Kempf T, Björklund E, Olofsson S, et al. Growth-differentiation factor-15 improves risk stratification in ST-segment elevation myocardial infarction. Eur Heart J. 2007;28:2858–2865.
   PubMed Web of Science ®Google Scholar
• Wollert KC, Kempf T, Peter T, et al. Prognostic value of growth-differentiation factor-15 in patients with non-ST-elevation acute coronary syndrome. Circulation. 2007;115:962–971.
   PubMed Web of Science ®Google Scholar
• Wollert KC, Kempf T, Lagerqvist B, et al. Growth differentiation factor 15 for risk stratification and selection of an invasive treatment strategy in non ST-elevation acute coronary syndrome. Circulation. 2007;116:1540–1548.
   PubMed Web of Science ®Google Scholar
• Fuernau G, Poenisch C, Eitel I, et al. Growth-differentiation factor 15 and osteoprotegerininacutemyocardialinfarction complicatedby cardiogenic shock: a biomarker substudy of the IABP-SHOCK IItrial. Eur J Heart Fail. 2014;16:880–887.
   PubMedGoogle Scholar
• Kempf T, Sinning JM, Quint A, et al. Growth-differentiation factor-15 for risk stratification in patients with stable and unstable coronary heart disease: results from the AtheroGene study. Circ Cardiovasc Genet. 2009;2:286–292.
   PubMed Web of Science ®Google Scholar
• Zhang S, Dai D, Wang X, et al. Growth differentiation factor-15 predicts the prognoses of patients with acute coronary syndrome: a meta-analysis. BMC Cardiovasc Disord. 2016;16:82.
   PubMed Web of Science ®Google Scholar
• Damman P, Kempf T, Windhausen F, et al. Growth-differentiation factor 15 for long-term prognostication in patients with non-ST-elevation acute coronary syndrome: an invasive versus conservative treatment in unstable coronary syndromes (ICTUS) substudy. Int J Cardiol. 2014;172:356–363.
   PubMed Web of Science ®Google Scholar
• Eggers KM, Kempf T, Lagerqvist B, et al. Growth-differentiation factor-15 for long-term risk prediction in patients stabilized after an episode of non-ST-segment-elevation acute coronary syndrome. Circ Cardiovasc Genet. 2010;3:88–96.
   PubMed Web of Science ®Google Scholar
• Eitel I, Blase P, Adams V, et al. Growth-differentiation factor 15 as predictor of mortality in acute reperfused ST-elevation myocardial infarction: insights from cardiovascular magnetic resonance. Heart. 2011;97:632–640.
   PubMed Web of Science ®Google Scholar
• Wallentin L, Lindhagen L, Ärnström E, et al. Early invasive versus non-invasive treatment in patients with non-ST-elevation acute coronary syndrome (FRISC-II): 15 year follow-up of a prospective, randomised, multicentre study. Lancet. 2016;388:1903–1911.
   PubMed Web of Science ®Google Scholar
• Duong Van Huyen JP, Cheval L, Bloch-Faure M, et al. GDF15 triggers homeostatic proliferation of acid secreting collecting duct cells. JASN. 2008;19:1965–1974.
   Web of Science ®Google Scholar
• Zimmers TA, Jin X, Hsiao EC, et al. Growth differentiation factor-15/macrophage inhibitory cytokine-1 induction after kidney and lung injury. Shock. 2005;23:543–548.
   PubMed Web of Science ®Google Scholar
• Martini S, Nair V, Keller BJ, et al. Integrative biology identifies shared transcriptional networks in CKD. JASN. 2014;25:2559–2572.
   Web of Science ®Google Scholar
• Roshanravan B, Khatri M, Robinson-Cohen C, et al. A prospective study of frailty in nephrology-referred patients with CKD. Am J Kidney Dis. 2012;60:912–921.
   PubMed Web of Science ®Google Scholar
• Roshanravan B, Robinson-Cohen C, Patel KV, et al. Association between physical performance and all-cause mortality in CKD. JASN. 2013;24:822–830.
   Web of Science ®Google Scholar
• Nair V, Robinson-Cohen C, Smith MR, et al. Growth differentiation factor-15 and risk of CKD progression. J Am Soc Nephrol. 2017;28:2233–2240.
   PubMed Web of Science ®Google Scholar
• Guenancia C, Kahli A, Laurent G, et al. Pre-operative growth differentiation factor 15 as a novel biomarker of acute kidney injury after cardiac bypass surgery. Int J Cardiol. 2015;197:66–71.
   PubMed Web of Science ®Google Scholar
• Kahli A, Guenancia C, Zeller M, et al. Growth differentiation factor-15 (GDF-15) levels are associated with cardiac and renal injury in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass. PLoS One. 2014;9:e105759.
   PubMed Web of Science ®Google Scholar
• Heringlake M, Charitos EI, Erber K, et al. Preoperative plasma growth-differentiation factor-15 for prediction of acute kidney injury in patients undergoing cardiac surgery. Crit Care. 2016;20:317.
   PubMed Web of Science ®Google Scholar
• Stehouwer CD, Fischer HR, van Kuijk AW, et al. Endothelial dysfunction precedes development of microalbuminuria in IDDM. Diabetes. 1995;44:561–564.
   PubMed Web of Science ®Google Scholar
• Sun L, Zhou X, Jiang J, et al. Growth differentiation factor-15 levels and the risk of contrast induced acute kidney injury in acute myocardial infarction patients treated invasively: a propensity-score match analysis. PLoS One. 2018;13:e0194152.
   PubMedGoogle Scholar
• Ho JE, Hwang SJ, Wollert KC, et al. Biomarkers of cardiovascular stress and incident chronic kidney disease. Clin Chem. 2013;59:1613–1620.
   PubMed Web of Science ®Google Scholar
• Breit SN, Carrero JJ, Tsai VW, et al. Macrophage inhibitory cytokine-1 (MIC-1/GDF15) and mortality in end-stage renal disease. Nephrol Dial Transplant. 2012;27:70–75.
   PubMed Web of Science ®Google Scholar
• Yilmaz H, Çelik HT, Gurel OM, et al. Increased serum levels of GDF-15 associated with mortality and subclinical atherosclerosis in patients on maintenance hemodialysis. Herz. 2015;40:305–312.
   PubMed Web of Science ®Google Scholar
• You AS, Kalantar-Zadeh K, Lerner L, et al. Association of growth differentiation factor 15 with mortality in a prospective hemodialysis cohort. Cardiorenal Med. 2017;7:158–168.
   PubMed Web of Science ®Google Scholar
• Bargenda A, Musiał K, Zwolińska D. Epidermal growth factor, growth differentiation factor-15, and survivin as novel biocompatibility markers in children on chronic dialysis. Biomarkers. 2016;21:752–756.
   PubMed Web of Science ®Google Scholar
• Taddei S, Virdis A. Growth differentiation factor-15 and cardiovascular dysfunction and disease: male factor or innocent bystander? Eur Heart J. 2010;31:1168–1171.
   PubMed Web of Science ®Google Scholar
• Bonaterra GA, Zügel S, Thogersen J, et al. Growth differentiation factor-15 deficiency inhibits atherosclerosis progression by regulating interleukin-6-dependent inflammatory response to vascular injury. J Am Heart Assoc. 2012;1:e002550.
   PubMed Web of Science ®Google Scholar
• Xu J, Kimball TR, Lorenz JN, et al. GDF15/MIC-1 functions as a protective and antihypertrophic factor released from the myocardium in association with SMAD protein activation. Circ Res. 2006;98:342–350.
   PubMed Web of Science ®Google Scholar
• Kalantar-Zadeh K, Balakrishnan VS. The kidney disease wasting: inflammation, oxidative stress, and diet-gene interaction. Hemodialysis Int. 2006;10:315–325.
   PubMedGoogle Scholar
• Frimodt-Møller M, von Scholten BJ, Reinhard H, et al. Growth differentiation factor-15 and fibroblast growth factor-23 are associated with mortality in type 2 diabetes – an observational follow-up study. PLoS One. 2018;13:e0196634.
   PubMed Web of Science ®Google Scholar
• Hellemons ME, Mazagova M, Gansevoort RT, et al. Growth-differentiation factor 15 predicts worsening of albuminuria in patients with type 2 diabetes. Diabetes Care. 2012;35:2340–2346.
   PubMed Web of Science ®Google Scholar
• Deckert T, Feldt-Rasmussen B, Borch Johnsen K, et al. Albuminuria reflects widespread vascular damage. The Steno hypothesis. Diabetologia. 1989;32:219–226.
   PubMed Web of Science ®Google Scholar
• Lajer M, Jorsal A, Tarnow L, et al. Plasma growth differentiation factor-15 independently predicts all-cause and cardiovascular mortality as well as deterioration of kidney function in type 1 diabetic patients with nephropathy. Diabetes Care. 2010;33:1567–1572.
   PubMed Web of Science ®Google Scholar
• Bidadkosh A, Lambooy SPH, Heerspink HJ, et al. Predictive properties of biomarkers GDF-15, NTproBNP, and hs-TnT for morbidity and mortality in patients with type 2 diabetes with nephropathy. Diabetes Care. 2017;40:784–792.
   PubMed Web of Science ®Google Scholar
• Kastritis E, Papassotiriou I, Merlini G, et al. Growth differentiation factor-15 is a new biomarker for survival and renal outcomes in light chain amyloidosis. Blood. 2018;131:1568–1575.
   PubMed Web of Science ®Google Scholar
• Teng J, Turbat-Herrera EA, Herrera GA. An animal model of glomerular light-chain-associated amyloidogenesis depicts the crucial role of lysosomes. Kidney Int. 2014;86:738–746.
   PubMed Web of Science ®Google Scholar
• Liao R, Jain M, Teller P, et al. Infusion of light chains from patients with cardiac amyloidosis causes diastolic dysfunction in isolated mouse hearts. Circulation. 2001;104:1594–1597.
   PubMed Web of Science ®Google Scholar
• Ham YR, Song CH, Bae HJ, et al. Growth differentiation factor-15 as a predictor of idiopathic membranous nephropathy progression: a retrospective study. Dis Markers. 2018;2018:1.
   Google Scholar
• Na KR, Kim YH, Chung HK, et al. Growth differentiation factor 15 as a predictor of adverse renal outcomes in patients with immunoglobulin A nephropathy. Intern Med J. 2017;47:1393–1399.
   PubMed Web of Science ®Google Scholar
• Zimmers TA, Jin X, Hsiao EC, et al. Growth differentiation factor-15: induction in liver injury through p53 and tumor necrosis factor-independent mechanisms. J Surg Res. 2006;130:45–51.
   PubMed Web of Science ®Google Scholar
• Kim KH, Kim SH, Han DH, et al. Growth differentiation factor 15 ameliorates nonalcoholic steatohepatitis and related metabolic disorders in mice. Sci Rep. 2018;8:6789.
   PubMed Web of Science ®Google Scholar
• Li D, Zhang H, Zhong Y. Hepatic GDF15 is regulated by CHOP of the unfolded protein response and alleviates NAFLD progression in obese mice. Biochem Biophys Res Commun. 2018;498:388–394.
   PubMed Web of Science ®Google Scholar
• Zhang M, Sun W, Qian J, et al. Fasting exacerbates hepatic growth differentiation factor 15 to promote fatty acid β-oxidation and ketogenesis via activating XBP1 signaling in liver. Redox Biol. 2018;16:87–96.
   PubMed Web of Science ®Google Scholar
• Chung HK, Kim JT, Kim HW, et al. GDF15 deficiency exacerbates chronic alcohol- and carbon tetrachloride-induced liver injury. Sci Rep. 2017;7:17238.
   PubMed Web of Science ®Google Scholar
• Dong G, Ma M, Lin X, et al. Treatment-damaged hepatocellular carcinoma promotes activities of hepatic stellate cells and fibrosis through GDF15. Exp Cell Res. 2018;370:468–477.
   PubMed Web of Science ®Google Scholar
• Koo BK, Um SH, Seo DS, et al. Growth differentiation factor 15 predicts advanced fibrosis in biopsy-proven non-alcoholic fatty liver disease. Liver Int. 2018;38:695–705.
   PubMed Web of Science ®Google Scholar
• Olsen OE, Skjaervik A, Størdal BF, et al. TGF-β contamination of purified recombinant GDF15. PLoS One. 2017;12:e0187349.
   PubMed Web of Science ®Google Scholar
• Krawczyk M, Zimmermann S, Hess G, et al. Panel of three novel serum markers predicts liver stiffness and fibrosis stages in patients with chronic liver disease. PLoS One. 2017;12:e0173506.
   PubMed Web of Science ®Google Scholar
• Liu X, Chi X, Gong Q, et al. Association of serum level of growth differentiation factor 15 with liver cirrhosis and hepatocellular carcinoma. PLoS One. 2015;10:e0127518.
   PubMed Web of Science ®Google Scholar
• Lee ES, Kim SH, Kim HJ, et al. Growth differentiation factor 15 predicts chronic liver disease severity. Gut Liver. 2017;11:276–282.
   PubMed Web of Science ®Google Scholar
• Si Y, Liu X, Cheng M, et al. Growth differentiation factor 15 is induced by hepatitis C virus infection and regulates hepatocellular carcinoma-related genes. PLoS One. 2011;6:e19967.
   PubMed Web of Science ®Google Scholar
• Ding Q, Mracek T, Gonzalez-Muniesa P, et al. Identification of macrophage inhibitory cytokine-1 in adipose tissue and its secretion as an adipokine by human adipocytes. Endocrinology. 2009;150:1688–1696.
   PubMed Web of Science ®Google Scholar
• Adela R, Banerjee SK. GDF-15 as a target and biomarker for diabetes and cardiovascular diseases: a translational prospective. J Diabetes Res. 2015;2015:490842.
   PubMed Web of Science ®Google Scholar
• Macia L, Tsai VW, Nguyen AD, et al. Macrophage inhibitory cytokine 1 (MIC-1/GDF15) decreases food intake, body weight and improves glucose tolerance in mice on normal & obesogenic diets. PLoS One. 2012;7:e34868.
   PubMed Web of Science ®Google Scholar
• Chung HK, Ryu D, Kim KS, et al. Growth differentiation factor 15 is a myomitokine governing systemic energy homeostasis. J Cell Biol. 2017;216:149–165.
   PubMed Web of Science ®Google Scholar
• Tran T, Yang J, Gardner J, et al. GDF15 deficiency promotes high fat diet-induced obesity in mice. PLoS One. 2018;13:e0201584.
   PubMed Web of Science ®Google Scholar
• Karczewska-Kupczewska M, Kowalska I, Nikolajuk A, et al. Hyperinsulinemia acutely increases serum macrophage inhibitory cytokine-1 concentration in anorexia nervosa and obesity. Clin Endocrinol (Oxf). 2012;76:46–50.
   PubMed Web of Science ®Google Scholar
• Schernthaner-Reiter MH, Kasses D, Tugendsam C, et al. Growth differentiation factor 15 increases following oral glucose ingestion = effect of meal composition and obesity. Eur J Endocrinol. 2016;175:623–631.
   PubMed Web of Science ®Google Scholar
• Dostálová I, Roubícek T, Bártlová M, et al. Increased serum concentrations of macrophage inhibitory cytokine-1 in patients with obesity and type 2 diabetes mellitus: the influence of very low calorie diet. Eur J Endocrinol. 2009;161:397–404.
   PubMed Web of Science ®Google Scholar
• Shariat A, Farhangi MA, Zeinalian R. Association between serum levels of vascular endothelial growth factor, macrophage inhibitory cytokine and markers of oxidative stress, with the metabolic syndrome and its components in obese individuals. Nutr Clin Métabol. 2018;32:95–101.
   Web of Science ®Google Scholar
• Vila G, Riedl M, Anderwald C, et al. The relationship between insulin resistance and the cardiovascular biomarker growth differentiation factor-15 in obese patients. Clin Chem. 2011;57:309–316.
   PubMed Web of Science ®Google Scholar
• Yuca SA, Cimbek EA, Şen Y, et al. The relationship between metabolic parameters, cardiac parameters and MIC-1/GDF15 in obese children. Exp Clin Endocrinol Diabetes. 2017;125:86–90.
   PubMed Web of Science ®Google Scholar
• Berberoglu Z, Aktas A, Fidan Y, et al. Plasma GDF-15 levels and their association with hormonal and metabolic status in women with polycystic ovary syndrome aged 25-35. Minerva Endocrinol. 2014;39:89–97.
   PubMed Web of Science ®Google Scholar
• Berberoglu Z, Aktas A, Fidan Y, et al. Association of plasma GDF-9 or GDF-15 levels with bone parameters in polycystic ovary syndrome. J Bone Miner Metab. 2015;33:101–108.
   PubMed Web of Science ®Google Scholar
• Li F, Ruan X, Min L. Targeting both sides of the GDF15-GFRAL-RET receptor complex: a new approach to achieve body weight homeostasis. Genes Dis. 2017;4:183–184.
   PubMed Web of Science ®Google Scholar
• Xiong Y, Walker K, Min X, et al. Long-acting MIC-1/GDF15 molecules to treat obesity: evidence from mice to monkeys. Sci Transl Med. 2017;9:412.
   Web of Science ®Google Scholar
• Villanueva MT. Obesity: GDF15 tells the brain to lose weight. Nat Rev Drug Discov. 2017;16:827.
   PubMed Web of Science ®Google Scholar
• Hong JH, Chung HK, Park HY, et al. GDF15 is a novel biomarker for impaired fasting glucose. Diabetes Metab J. 2014;38:472–479.
   PubMedGoogle Scholar
• Yalcin MM, Altinova AE, Akturk M, et al. GDF-15 and hepcidin levels in nonanemic patients with impaired glucose tolerance. J Diabetes Res. 2016;2016:1.
   Google Scholar
• Bao X, Borné Y, Muhammad IF, et al. Growth differentiation factor 15 is positively associated with incidence of diabetes mellitus: the Malmö Diet and Cancer-Cardiovascular Cohort. Diabetologia. 2019;62:78–86.
   PubMed Web of Science ®Google Scholar
• Germain RN. Maintaining system homeostasis: the third law of Newtonian immunology. Nat Immunol. 2012;13:902–906.
   PubMed Web of Science ®Google Scholar
• Kolb H, Mandrup-Poulsen T. The global diabetes epidemic as a consequence of lifestyle-induced low-grade inflammation. Diabetologia. 2010;53:10–20.
   PubMed Web of Science ®Google Scholar
• Kelly JA, Lucia MS, Lambert JR. p53 Controls prostate-derived factor/macrophage inhibitory cytokine/NSAID-activated gene expression in response to cell density, DNA damage and hypoxia through diverse mechanisms. Cancer Lett. 2009;277:38–47.
   PubMed Web of Science ®Google Scholar
• Resl M, Clodi M, Vila G, et al. Targeted multiple biomarker approach in predicting cardiovascular events in patients with diabetes. Heart. 2016;102:1963–1968.
   PubMed Web of Science ®Google Scholar
• Shin MY, Kim JM, Kang YE, et al. Association between growth differentiation factor 15 (GDF15) and cardiovascular risk in patients with newly diagnosed type 2 diabetes mellitus. J Korean Med Sci. 2016;31:1413–1418.
   PubMed Web of Science ®Google Scholar
• Li J, Yang L, Qin W, et al. Adaptive induction of growth differentiation factor 15 attenuates endothelial cell apoptosis in response to high glucose stimulus. PLoS One. 2013;8:e65549.
   PubMed Web of Science ®Google Scholar
• Gerstein HC, Pare G, Hess S, et al. Growth differentiation factor 15 as a novel biomarker for metformin. Diabetes Care. 2017;40:280–283.
   PubMed Web of Science ®Google Scholar
• Mueller T, Leitner I, Egger M, et al. Association of the biomarkers soluble ST2, galectin-3 and growth-differentiation factor-15 with heart failure and other non-cardiac diseases. Clin Chim Acta. 2015;445:155–160.
   PubMed Web of Science ®Google Scholar
• Dieplinger B, Egger M, Leitner I, et al. Interleukin 6, galectin 3, growth differentiation factor 15, and soluble ST2 for mortality prediction in critically ill patients. J Crit Care. 2016;34:38–45.
   PubMed Web of Science ®Google Scholar
• Buendgens L, Yagmur E, Bruensing J, et al. Growth differentiation factor-15 is a predictor of mortality in critically ill patients with sepsis. Dis Markers. 2017;2017:5271203.
   PubMed Web of Science ®Google Scholar
• Bloch SA, Lee JY, Syburra T, et al. Increased expression of GDF-15 may mediate ICU acquired weakness by down-regulating muscle microRNAs. Thorax. 2015;70:219–228.
   PubMed Web of Science ®Google Scholar
• Tanno T, Bhanu NV, Oneal PA, et al. High levels of GDF15 in thalassemia suppress expression of the iron regulatory protein hepcidin. Nat Med. 2007;13:1096–1101.
   PubMed Web of Science ®Google Scholar
• Tanno T, Noel P, Miller JL. Growth differentiation factor 15 in erythroid health and disease. Curr Opin Hematol. 2010;17:184–190.
   PubMed Web of Science ®Google Scholar
• Lakhal S, Talbot NP, Crosby A, et al. Regulation of growth differentiation factor 15 expression by intracellular iron. Blood. 2009;113:1555–1563.
   PubMed Web of Science ®Google Scholar
• Theurl I, Finkenstedt A, Schroll A, et al. Growth differentiation factor 15 in anaemia of chronic disease, iron deficiency anaemia and mixed type anaemia. Br J Haematol. 2010;148:449–455.
   PubMed Web of Science ®Google Scholar
• Ronzoni L, Sonzogni L, Duca L, et al. Growth differentiation factor 15 expression and regulation during erythroid differentiation in non-transfusion dependent thalassemia. Blood Cells Mol Dis. 2015;54:26–28.
   PubMed Web of Science ®Google Scholar
• Athiyarath R, George B, Mathews V, et al. Association of growth differentiation factor 15 (GDF15) polymorphisms with serum GDF15 and ferritin levels in β-thalassemia. Ann Hematol. 2014;93:2093–2095.
   PubMed Web of Science ®Google Scholar
• Lukaszyk E, Lukaszyk M, Koc-Zorawska E, et al. GDF-15, iron, and inflammation in early chronic kidney disease among elderly patients. Int Urol Nephrol. 2016;48:839–844.
   PubMed Web of Science ®Google Scholar
• Li XY, Ying J, Li JH, et al. Growth differentiation factor GDF-15 does not influence iron metabolism in stable chronic haemodialysis patients. Ann Clin Biochem. 2015;52:399–403.
   PubMed Web of Science ®Google Scholar
• Malyszko J, Koc-Zorawska E, Malyszko JS, et al. GDF15 is related to anemia and hepcidin in kidney allograft recipients. Nephron Clin Pract. 2013;123:112–117.
   PubMed Web of Science ®Google Scholar
• Przybyłowski P, Wasilewski G, Bachorzewska-Gajewska H, et al. Growth differentiation factor 15 is related to anemia and iron metabolism in heart allograft recipients and patients with chronic heart failure. Transplant Proc. 2014;46:2852–2855.
   PubMed Web of Science ®Google Scholar