Tubular cells produce FGF2 via autophagy after acute kidney injury leading to fibroblast activation and renal fibrosis

References

• Ronco C, Bellomo R, Kellum JA. Acute kidney injury. Lancet. 2019;394:1949–1964.
   PubMed Web of Science ®Google Scholar
• Mehta RL, Burdmann EA, Cerda J, et al. Recognition and management of acute kidney injury in the International Society of Nephrology 0by25 global snapshot: a multinational cross-sectional study. Lancet. 2016;387:2017–2025.
   PubMed Web of Science ®Google Scholar
• See EJ, Jayasinghe K, Glassford N, et al. Long-term risk of adverse outcomes after acute kidney injury: a systematic review and meta-analysis of cohort studies using consensus definitions of exposure. Kidney Int. 2019;95:160–172.
   PubMed Web of Science ®Google Scholar
• Chawla LS, Eggers PW, Star RA, et al. Acute kidney injury and chronic kidney disease as interconnected syndromes. N Engl J Med. 2014;371:58–66.
   PubMed Web of Science ®Google Scholar
• Coca SG, Singanamala S, Parikh CR. Chronic kidney disease after acute kidney injury: a systematic review and meta-analysis. Kidney Int. 2012;81:442–448.
   PubMed Web of Science ®Google Scholar
• Hsu CY. Yes, AKI truly leads to CKD. J Am Soc Nephrol. 2012;23:967–969.
   PubMed Web of Science ®Google Scholar
• Ferenbach DA, Bonventre JV. Mechanisms of maladaptive repair after AKI leading to accelerated kidney ageing and CKD. Nat Rev Nephrol. 2015;11:264–276.
   PubMed Web of Science ®Google Scholar
• Venkatachalam MA, Weinberg JM, Kriz W, et al. Failed tubule recovery, AKI-CKD transition, and kidney disease progression. J Am Soc Nephrol. 2015;26:1765–1776.
   PubMed Web of Science ®Google Scholar
• Basile DP, Bonventre JV, Mehta R, et al. Progression after aki: understanding maladaptive repair processes to predict and identify therapeutic treatments. J Am Soc Nephrol. 2016;27:687–697.
   PubMed Web of Science ®Google Scholar
• Kumar S. Cellular and molecular pathways of renal repair after acute kidney injury. Kidney Int. 2018;93:27–40.
   PubMed Web of Science ®Google Scholar
• Humphreys BD. Mechanisms of renal fibrosis. Annu Rev Physiol. 2018;80:309–326.
   PubMed Web of Science ®Google Scholar
• Liu BC, Tang TT, Lv LL, et al. Renal tubule injury: a driving force toward chronic kidney disease. Kidney Int. 2018;93:568–579.
   PubMed Web of Science ®Google Scholar
• Grgic I, Campanholle G, Bijol V, et al. Targeted proximal tubule injury triggers interstitial fibrosis and glomerulosclerosis. Kidney Int. 2012;82:172–183.
   PubMed Web of Science ®Google Scholar
• Takaori K, Nakamura J, Yamamoto S, et al. Severity and frequency of proximal tubule injury determines renal prognosis. J Am Soc Nephrol. 2016;27:2393–2406.
   PubMed Web of Science ®Google Scholar
• Humphreys BD, Xu F, Sabbisetti V, et al. Chronic epithelial kidney injury molecule-1 expression causes murine kidney fibrosis. J Clin Invest. 2013;123:4023–4035.
   PubMed Web of Science ®Google Scholar
• Geng H, Lan R, Wang G, et al. Inhibition of autoregulated TGFbeta signaling simultaneously enhances proliferation and differentiation of kidney epithelium and promotes repair following renal ischemia. Am J Pathol. 2009;174:1291–1308.
   PubMed Web of Science ®Google Scholar
• Lan R, Geng H, Polichnowski AJ, et al. PTEN loss defines a TGF-beta-induced tubule phenotype of failed differentiation and JNK signaling during renal fibrosis. Am J Physiol Renal Physiol. 2012;302:F1210–1223.
   PubMed Web of Science ®Google Scholar
• Geng H, Lan R, Singha PK, et al. Lysophosphatidic acid increases proximal tubule cell secretion of profibrotic cytokines PDGF-B and CTGF through LPA2- and Galphaq-mediated Rho and alphavbeta6 integrin-dependent activation of TGF-beta. Am J Pathol. 2012;181:1236–1249.
   PubMed Web of Science ®Google Scholar
• Lan R, Geng H, Singha PK, et al. Mitochondrial pathology and glycolytic shift during proximal tubule atrophy after ischemic AKI. J Am Soc Nephrol. 2016;27:3356–3367.
   PubMed Web of Science ®Google Scholar
• Kang HM, Ahn SH, Choi P, et al. Defective fatty acid oxidation in renal tubular epithelial cells has a key role in kidney fibrosis development. Nat Med. 2015;21:37–46.
   PubMed Web of Science ®Google Scholar
• Yang L, Besschetnova TY, Brooks CR, et al. Epithelial cell cycle arrest in G2/M mediates kidney fibrosis after injury. Nat Med. 2010;16:535–543, 1p following 143.
   PubMed Web of Science ®Google Scholar
• Mizushima N. A brief history of autophagy from cell biology to physiology and disease. Nat Cell Biol. 2018;20:521–527.
   PubMed Web of Science ®Google Scholar
• Tang C, Livingston MJ, Liu Z, et al. Autophagy in kidney homeostasis and disease. Nat Rev Nephrol. 2020;16:489–508.
   PubMed Web of Science ®Google Scholar
• Choi ME. Autophagy in kidney disease. Annu Rev Physiol. 2020;82:297–322.
   PubMed Web of Science ®Google Scholar
• Huber TB, Edelstein CL, Hartleben B, et al. Emerging role of autophagy in kidney function, diseases and aging. Autophagy. 2012;8:1009–1031.
   PubMed Web of Science ®Google Scholar
• Kimura T, Takabatake Y, Takahashi A, et al. Autophagy protects the proximal tubule from degeneration and acute ischemic injury. J Am Soc Nephrol. 2011;22:902–913.
   PubMed Web of Science ®Google Scholar
• Liu S, Hartleben B, Kretz O, et al. Autophagy plays a critical role in kidney tubule maintenance, aging and ischemia-reperfusion injury. Autophagy. 2012;8:826–837.
   PubMed Web of Science ®Google Scholar
• Jiang M, Wei Q, Dong G, et al. Autophagy in proximal tubules protects against acute kidney injury. Kidney Int. 2012;82:1271–1283.
   PubMed Web of Science ®Google Scholar
• Takahashi A, Kimura T, Takabatake Y, et al. Autophagy guards against cisplatin-induced acute kidney injury. Am J Pathol. 2012;180:517–525.
   PubMed Web of Science ®Google Scholar
• Kaushal GP, Shah SV. Autophagy in acute kidney injury. Kidney Int. 2016;89:779–791.
   PubMed Web of Science ®Google Scholar
• Li L, Wang ZV, Hill JA, et al. New autophagy reporter mice reveal dynamics of proximal tubular autophagy. J Am Soc Nephrol. 2014;25:305–315.
   PubMed Web of Science ®Google Scholar
• Brooks CR, Yeung MY, Brooks YS, et al. KIM-1-/TIM-1-mediated phagocytosis links ATG5-/ULK1-dependent clearance of apoptotic cells to antigen presentation. EMBO J. 2015;34:2441–2464.
   PubMed Web of Science ®Google Scholar
• Sharfuddin AA, Molitoris BA. Pathophysiology of ischemic acute kidney injury. Nat Rev Nephrol. 2011;7:189–200.
   PubMed Web of Science ®Google Scholar
• Bonventre JV, Yang L. Cellular pathophysiology of ischemic acute kidney injury. J Clin Invest. 2011;121:4210–4221.
   PubMed Web of Science ®Google Scholar
• Fu Y, Cai J, Li F, et al. Chronic effects of repeated low-dose cisplatin treatment in mouse kidneys and renal tubular cells. Am J Physiol Renal Physiol. 2019;317:F1582–F1592.
   PubMed Web of Science ®Google Scholar
• Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, et al. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)(1). Autophagy. 2021;17:1–382.
   PubMed Web of Science ®Google Scholar
• Livingston MJ, Ding HF, Huang S, et al. Persistent activation of autophagy in kidney tubular cells promotes renal interstitial fibrosis during unilateral ureteral obstruction. Autophagy. 2016;12:976–998.
   PubMed Web of Science ®Google Scholar
• Ma Z, Li L, Livingston MJ, et al. p53/microRNA-214/ULK1 axis impairs renal tubular autophagy in diabetic kidney disease. J Clin Invest. 2020;130:5011–5026.
   PubMed Web of Science ®Google Scholar
• Traykova-Brauch M, Schonig K, Greiner O, et al. An efficient and versatile system for acute and chronic modulation of renal tubular function in transgenic mice. Nat Med. 2008;14:979–984.
   PubMed Web of Science ®Google Scholar
• Schonig K, Schwenk F, Rajewsky K, et al. Stringent doxycycline dependent control of CRE recombinase in vivo. Nucleic Acids Res. 2002;30:e134.
   PubMed Web of Science ®Google Scholar
• Polichnowski AJ, Lan R, Geng H, et al. Severe renal mass reduction impairs recovery and promotes fibrosis after AKI. J Am Soc Nephrol. 2014;25:1496–1507.
   PubMed Web of Science ®Google Scholar
• Baisantry A, Bhayana S, Rong S, et al. Autophagy induces prosenescent changes in proximal tubular S3 segments. J Am Soc Nephrol. 2016;27:1609–1616.
   PubMed Web of Science ®Google Scholar
• Mylonas KJ, O’Sullivan ED, Humphries D, et al. Cellular senescence inhibits renal regeneration after injury in mice, with senolytic treatment promoting repair. Sci Transl Med. 2021;13:eabb0203. doi:10.1126/scitranslmed.abb0203.
   PubMed Web of Science ®Google Scholar
• Li L, Kang H, Zhang Q, et al. FoxO3 activation in hypoxic tubules prevents chronic kidney disease. J Clin Invest. 2019;129:2374–2389.
   PubMed Web of Science ®Google Scholar
• Shu S, Zhu J, Liu Z, et al. Endoplasmic reticulum stress is activated in post-ischemic kidneys to promote chronic kidney disease. EBioMedicine. 2018;37:269–280.
   PubMed Web of Science ®Google Scholar
• Ding Y, Kim S, Lee SY, et al. Autophagy regulates TGF-beta expression and suppresses kidney fibrosis induced by unilateral ureteral obstruction. J Am Soc Nephrol. 2014;25:2835–2846.
   PubMed Web of Science ®Google Scholar
• Li H, Peng X, Wang Y, et al. Atg5-mediated autophagy deficiency in proximal tubules promotes cell cycle G2/M arrest and renal fibrosis. Autophagy. 2016;12:1472–1486.
   PubMed Web of Science ®Google Scholar
• Gewin LS. Renal fibrosis: primacy of the proximal tubule. Matrix Biol. 2018;68-69:248–262.
   PubMed Web of Science ®Google Scholar
• He L, Livingston MJ, Dong Z. Autophagy in acute kidney injury and repair. Nephron Clin Pract. 2014;127:56–60.
   PubMedGoogle Scholar
• Canaud G, Brooks CR, Kishi S, et al. Cyclin G1 and TASCC regulate kidney epithelial cell G2-M arrest and fibrotic maladaptive repair. Sci Transl Med. 2019;11. DOI:10.1126/scitranslmed.aav4754.
   PubMed Web of Science ®Google Scholar
• Narita M, Young AR, Arakawa S, et al. Spatial coupling of mTOR and autophagy augments secretory phenotypes. Science. 2011;332:966–970.
   PubMed Web of Science ®Google Scholar
• Malaquin N, Martinez A, Rodier F. Keeping the senescence secretome under control: molecular reins on the senescence-associated secretory phenotype. Exp Gerontol. 2016;82:39–49.
   PubMed Web of Science ®Google Scholar
• New J, Thomas SM. Autophagy-dependent secretion: mechanism, factors secreted, and disease implications. Autophagy. 2019;15:1682–1693.
   PubMed Web of Science ®Google Scholar
• Ponpuak M, Mandell MA, Kimura T, et al. Secretory autophagy. Curr Opin Cell Biol. 2015;35:106–116.
   PubMed Web of Science ®Google Scholar
• Bernard M, Dieude M, Yang B, et al. Autophagy fosters myofibroblast differentiation through MTORC2 activation and downstream upregulation of CTGF. Autophagy. 2014;10:2193–2207.
   PubMed Web of Science ®Google Scholar
• Nuchel J, Ghatak S, Zuk AV, et al. TGFB1 is secreted through an unconventional pathway dependent on the autophagic machinery and cytoskeletal regulators. Autophagy. 2018;14:465–486.
   PubMed Web of Science ®Google Scholar
• Leidal AM, Huang HH, Marsh T, et al. The LC3-conjugation machinery specifies the loading of RNA-binding proteins into extracellular vesicles. Nat Cell Biol. 2020;22:187–199.
   PubMed Web of Science ®Google Scholar
• Kimura T, Jia J, Kumar S, et al. Dedicated SNAREs and specialized TRIM cargo receptors mediate secretory autophagy. EMBO J. 2017;36:42–60.
   PubMed Web of Science ®Google Scholar
• Komatsu M, Waguri S, Ueno T, et al. Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice. J Cell Biol. 2005;169:425–434.
   PubMed Web of Science ®Google Scholar
• Section 2: AKI definition. Kidney Int Suppl. 2012;2:19–36.
   Web of Science ®Google Scholar
• Fan Y, Xiao W, Lee K, et al. Inhibition of reticulon-1A-mediated endoplasmic reticulum stress in early AKI attenuates renal fibrosis development. J Am Soc Nephrol. 2017;28:2007–2021.
   PubMed Web of Science ®Google Scholar
• Sinha D, Wang Z, Price VR, et al. Chemical anoxia of tubular cells induces activation of c-Src and its translocation to the zonula adherens. Am J Physiol Renal Physiol. 2003;284:F488–497.
   PubMed Web of Science ®Google Scholar
• Livingston MJ, Wang J, Zhou J, et al. Clearance of damaged mitochondria via mitophagy is important to the protective effect of ischemic preconditioning in kidneys. Autophagy. 2019;15:2142–2162.
   PubMed Web of Science ®Google Scholar
• Wei Q, Sun H, Song S, et al. MicroRNA-668 represses MTP18 to preserve mitochondrial dynamics in ischemic acute kidney injury. J Clin Invest. 2018;128:5448–5464.
   PubMed Web of Science ®Google Scholar
• Racusen LC, Solez K, Colvin RB, et al. The Banff 97 working classification of renal allograft pathology. Kidney Int. 1999;55:713–723.
   PubMed Web of Science ®Google Scholar