Perspectives on the role of PTEN in diabetic nephropathy: an update

References

• International Diabetes Federation. IDF diabetes atlas. 8th ed. Brussels (Belgium): International Diabetes Federation; 2017. Available from: http://www.diabetesatlas.org
   Google Scholar
• Zheng Y, Ley SH, Hu FB. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat Rev Endocrinol. 2018;14:88–98.
   PubMed Web of Science ®Google Scholar
• Gheith O, Farouk N, Nampoory N, et al. Diabetic kidney disease: world wide difference of prevalence and risk factors. J Nephropharmacol. 2016;5:49.
   PubMedGoogle Scholar
• Tesch GH. Diabetic nephropathy – is this an immune disorder? Clin Sci. 2017;131:2183–2199.
   PubMed Web of Science ®Google Scholar
• Wada J, Makino H. Inflammation and the pathogenesis of diabetic nephropathy. Clin Sci. 2013;124:139–152.
   PubMed Web of Science ®Google Scholar
• Liu Y. Cellular and molecular mechanisms of renal fibrosis. Nat Rev Nephrol. 2011;7:684–696.
   PubMed Web of Science ®Google Scholar
• Tojo A, Asaba K, Onozato ML. Suppressing renal NADPH oxidase to treat diabetic nephropathy. Expert Opin Ther Targets. 2007;11:1011–1018.
   PubMed Web of Science ®Google Scholar
• Noh H, King GL. The role of protein kinase C activation in diabetic nephropathy. Kidney Int Suppl. 2007;72:S49–S53.
   Google Scholar
• Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature. 2001;414:813–820.
   PubMed Web of Science ®Google Scholar
• Ahmad J. Management of diabetic nephropathy: recent progress and future perspective. Diabetes Metab Syndr Clin Res Rev. 2015;9:343–358.
   PubMed Web of Science ®Google Scholar
• Sharaf El Din UAA, Mansour Salem M, Abdulazim DO. Recent advances in management of diabetic nephropathy. J Clin Exp Nephrol. 2017 [cited 2018 Dec 30]. DOI:10.21767/2472-5056.100035
   Google Scholar
• Velagapudi C, Bhandari BS, Abboud-Werner S, et al. The tuberin/mTOR pathway promotes apoptosis of tubular epithelial cells in diabetes. J Am Soc Nephrol JASN. 2011;22:262–273.
   PubMed Web of Science ®Google Scholar
• Haneda M, Utsunomiya K, Koya D, et al. A new classification of Diabetic Nephropathy 2014: a report from Joint Committee on Diabetic Nephropathy. J. Diabetes Investig. 2015;6:242–246.
   PubMed Web of Science ®Google Scholar
• Yan R, Wang Y, Shi M, et al. Regulation of PTEN/AKT/FAK pathways by PPARγ impacts on fibrosis in diabetic nephropathy: YAN et al. J Cell Biochem. 2019;120(5):6998–7014.
   Web of Science ®Google Scholar
• Keniry M, Parsons R. The role of PTEN signaling perturbations in cancer and in targeted therapy. Oncogene. 2008;27:5477–5485.
   PubMed Web of Science ®Google Scholar
• Lee Y-R, Chen M, Pandolfi PP. The functions and regulation of the PTEN tumour suppressor: new modes and prospects. Nat Rev Mol Cell Biol. 2018;19:547–562.
   PubMed Web of Science ®Google Scholar
• Salmena L, Carracedo A, Pandolfi PP. Tenets of PTEN tumor suppression. Cell. 2008;133:403–414.
   PubMed Web of Science ®Google Scholar
• Li J, Yen C, Liaw D, et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science. 1997;275:1943–1947.
   PubMed Web of Science ®Google Scholar
• Steck PA, Pershouse MA, Jasser SA, et al. Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat Genet. 1997;15:356–362.
   PubMed Web of Science ®Google Scholar
• Gao J, Aksoy BA, Dogrusoz U, et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal. 2013;6:pl1.
   PubMed Web of Science ®Google Scholar
• Cerami E, Gao J, Dogrusoz U, et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2012;2:401–404.
   PubMed Web of Science ®Google Scholar
• Li DM, Sun H. TEP1, encoded by a candidate tumor suppressor locus, is a novel protein tyrosine phosphatase regulated by transforming growth factor beta. Cancer Res. 1997;57:2124–2129.
   PubMed Web of Science ®Google Scholar
• Myers MP, Pass I, Batty IH, et al. The lipid phosphatase activity of PTEN is critical for its tumor supressor function. Proc Natl Acad Sci USA. 1998;95:13513–13518.
   PubMed Web of Science ®Google Scholar
• Hopkins BD, Hodakoski C, Barrows D, et al. PTEN function: the long and the short of it. Trends Biochem Sci. 2014;39:183–190.
   PubMed Web of Science ®Google Scholar
• Tamura M, Gu J, Matsumoto K, et al. Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor PTEN. Science. 1998;280:1614–1617.
   PubMed Web of Science ®Google Scholar
• Zhou X, Hampel H, Thiele H, et al. Association of germline mutation in the PTEN tumour suppressor gene and Proteus and Proteus-like syndromes. Lancet Lond Engl. 2001;358(9277):210–211.
   PubMed Web of Science ®Google Scholar
• Yehia L, Ngeow J, Eng C. PTEN-opathies: from biological insights to evidence-based precision medicine. J Clin Invest. 2019;129:452–464.
   PubMed Web of Science ®Google Scholar
• Mayo LD, Donner DB. The PTEN, Mdm2, p53 tumor suppressor-oncoprotein network. Trends Biochem Sci. 2002;27:462–467.
   PubMed Web of Science ®Google Scholar
• Leslie NR, Yang X, Downes CP, et al. PtdIns(3,4,5)P(3)-dependent and -independent roles for PTEN in the control of cell migration. Curr Biol CB. 2007;17:115–125.
   PubMed Web of Science ®Google Scholar
• Bell CG, Teschendorff AE, Rakyan VK, et al. Genome-wide DNA methylation analysis for diabetic nephropathy in type 1 diabetes mellitus. BMC Med Genomics. 2010;3:33.
   PubMed Web of Science ®Google Scholar
• Ishihara H, Sasaoka T, Kagawa S, et al. Association of the polymorphisms in the 5′-untranslated region of PTEN gene with type 2 diabetes in a Japanese population. FEBS Lett. 2003;554:450–454.
   PubMed Web of Science ®Google Scholar
• Grinder-Hansen L, Ribel-Madsen R, Wojtaszewski JFP, et al. A common variation of the PTEN gene is associated with peripheral insulin resistance. Diabetes Metab. 2016;42:280–284.
   PubMed Web of Science ®Google Scholar
• Hansen L, Jensen JN, Ekstrøm CT, et al. Studies of variability in the PTEN gene among Danish caucasian patients with Type II diabetes mellitus. Diabetologia. 2001;44:237–240.
   PubMedGoogle Scholar
• Boucher J, Kleinridders A, Kahn CR. Insulin receptor signaling in normal and insulin-resistant states. Cold Spring Harb Perspect Biol. 2014;6(1):a009191–a009191.
   PubMed Web of Science ®Google Scholar
• Copps KD, White MF. Regulation of insulin sensitivity by serine/threonine phosphorylation of insulin receptor substrate proteins IRS1 and IRS2. Diabetologia. 2012;55:2565–2582.
   PubMed Web of Science ®Google Scholar
• Long YC, Cheng Z, Copps KD, et al. Insulin receptor substrates Irs1 and Irs2 coordinate skeletal muscle growth and metabolism via the Akt and AMPK pathways. Mol Cell Biol. 2011;31:430–441.
   PubMed Web of Science ®Google Scholar
• Ciaraldi TP, Nikoulina SE, Bandukwala RA, et al. Role of glycogen synthase kinase-3 alpha in insulin action in cultured human skeletal muscle cells. Endocrinology. 2007;148:4393–4399.
   PubMed Web of Science ®Google Scholar
• MacAulay K, Doble BW, Patel S, et al. Glycogen synthase kinase 3alpha-specific regulation of murine hepatic glycogen metabolism. Cell Metab. 2007;6:329–337.
   PubMed Web of Science ®Google Scholar
• Gupta A, Dey CS. PTEN and SHIP2 regulates PI3K/Akt pathway through focal adhesion kinase⋆. Mol Cell Endocrinol. 2009;309:55–62.
   PubMed Web of Science ®Google Scholar
• Khorami SAH, Huzwah K, Mutalib A, et al. PI3K/AKT pathway in modulating glucose homeostasis and its alteration in diabetes. AMBS. 2015;1(2):46–55.
   Google Scholar
• Nakashima N, Sharma PM, Imamura T, et al. The tumor suppressor PTEN negatively regulates insulin signaling in 3T3-L1 adipocytes. J Biol Chem. 2000;275:12889–12895.
   PubMed Web of Science ®Google Scholar
• Li A, Qiu M, Zhou H, et al. PTEN, insulin resistance and cancer. Curr Pharm Des. 2017;23:3667–3676.
   PubMed Web of Science ®Google Scholar
• Tang X, Powelka AM, Soriano NA, et al. PTEN, but not SHIP2, suppresses insulin signaling through the phosphatidylinositol 3-kinase/Akt pathway in 3T3-L1 adipocytes. J Biol Chem. 2005;280:22523–22529.
   PubMed Web of Science ®Google Scholar
• Mosser VA, Li Y, Quon MJ. PTEN does not modulate GLUT4 translocation in rat adipose cells under physiological conditions. Biochem Biophys Res Commun. 2001;288(4):1011–1017.
   PubMed Web of Science ®Google Scholar
• Pal A, Barber TM, Van de Bunt M, et al. PTEN mutations as a cause of constitutive insulin sensitivity and obesity. N Engl J Med. 2012;367:1002–1011.
   PubMed Web of Science ®Google Scholar
• Baumgartener JW. SHIP2: an emerging target for the treatment of type 2 diabetes mellitus. Curr Drug Targets Immune Endocr Metab Disord. 2003;3:291–298.
   PubMedGoogle Scholar
• Pagtalunan ME, Miller PL, Jumping-Eagle S, et al. Podocyte loss and progressive glomerular injury in type II diabetes. J Clin Invest. 1997;99:342–348.
   PubMed Web of Science ®Google Scholar
• Wharram BL. Podocyte depletion causes glomerulosclerosis: diphtheria toxin-induced podocyte depletion in rats expressing human diphtheria toxin receptor transgene. J Am Soc Nephrol. 2005;16:2941–2952.
   PubMed Web of Science ®Google Scholar
• Estacio RO, Schrier RW. Diabetic nephropathy: pathogenesis, diagnosis, and prevention of progression. Adv Intern Med. 2001;46:359–408.
   PubMedGoogle Scholar
• Lieberthal W, Levine JS. The role of the mammalian target of rapamycin (mTOR) in renal disease. J Am Soc Nephrol. 2009;20:2493–2502.
   PubMed Web of Science ®Google Scholar
• Kume S, Koya D, Uzu T, et al. Role of nutrient-sensing signals in the pathogenesis of diabetic nephropathy. BioMed Res Int. 2014;2014:315494.
   PubMed Web of Science ®Google Scholar
• Um SH, D’Alessio D, Thomas G. Nutrient overload, insulin resistance, and ribosomal protein S6 kinase 1, S6K1. Cell Metab. 2006;3:393–402.
   PubMed Web of Science ®Google Scholar
• Tzatsos A, Kandror KV. Nutrients suppress phosphatidylinositol 3-kinase/Akt signaling via raptor-dependent mTOR-mediated insulin receptor substrate 1 phosphorylation. Mol Cell Biol. 2006;26:63–76.
   PubMed Web of Science ®Google Scholar
• Zhang HH, Huang J, Düvel K, et al. Insulin stimulates adipogenesis through the Akt-TSC2-mTORC1 pathway. PLOS One. 2009;4:e6189.
   PubMed Web of Science ®Google Scholar
• Haruta T, Uno T, Kawahara J, et al. A rapamycin-sensitive pathway down-regulates insulin signaling via phosphorylation and proteasomal degradation of insulin receptor substrate-1. Mol Endocrinol. 2000;14:783–794.
   PubMed Web of Science ®Google Scholar
• Feliers D, Duraisamy S, Faulkner JL, et al. Activation of renal signaling pathways in db/db mice with type 2 diabetes. Kidney Int. 2001;60:495–504.
   PubMed Web of Science ®Google Scholar
• Chen J-K, Chen J, Thomas G, et al. S6 kinase 1 knockout inhibits uninephrectomy- or diabetes-induced renal hypertrophy. Am J Physiol-Ren Physiol. 2009;297:F585–F593.
   PubMed Web of Science ®Google Scholar
• Sakaguchi M, Isono M, Isshiki K, et al. Inhibition of mTOR signaling with rapamycin attenuates renal hypertrophy in the early diabetic mice. Biochem Biophys Res Commun. 2006;340:296–301.
   PubMed Web of Science ®Google Scholar
• Herbach N, Schairer I, Blutke A, et al. Diabetic kidney lesions of GIPR dn transgenic mice: podocyte hypertrophy and thickening of the GBM precede glomerular hypertrophy and glomerulosclerosis. Am J Physiol-Ren Physiol. 2009;296:F819–F829.
   PubMed Web of Science ®Google Scholar
• Inoki K, Mori H, Wang J, et al. mTORC1 activation in podocytes is a critical step in the development of diabetic nephropathy in mice. J Clin Invest. 2011;121:2181–2196.
   PubMed Web of Science ®Google Scholar
• Gödel M, Hartleben B, Herbach N, et al. Role of mTOR in podocyte function and diabetic nephropathy in humans and mice. J Clin Invest. 2011;121:2197–2209.
   PubMed Web of Science ®Google Scholar
• Fogo AB. The targeted podocyte. J Clin Invest. 2011;121:2142–2145.
   PubMed Web of Science ®Google Scholar
• Liliental J, Moon SY, Lesche R, et al. Genetic deletion of the Pten tumor suppressor gene promotes cell motility by activation of Rac1 and Cdc42 GTPases. Curr Biol CB. 2000;10:401–404.
   PubMed Web of Science ®Google Scholar
• Zhu J, Sun N, Aoudjit L, et al. Nephrin mediates actin reorganization via phosphoinositide 3-kinase in podocytes. Kidney Int. 2008;73:556–566.
   PubMed Web of Science ®Google Scholar
• Mahimainathan L, Das F, Venkatesan B, et al. Mesangial cell hypertrophy by high glucose is mediated by downregulation of the tumor suppressor PTEN. Diabetes. 2006;55:2115–2125.
   PubMed Web of Science ®Google Scholar
• Kato M, Putta S, Wang M, et al. TGF-β activates Akt kinase through a microRNA-dependent amplifying circuit targeting PTEN. Nat. Cell Biol. 2009;11:881–889.
   PubMed Web of Science ®Google Scholar
• Lin JS, Shi Y, Peng H, et al. Loss of PTEN promotes podocyte cytoskeletal rearrangement, aggravating diabetic nephropathy: podocyte PTEN in diabetic nephropathy. J Pathol. 2015;236:30–40.
   PubMed Web of Science ®Google Scholar
• Wang J-Y, Gao Y-B, Zhang N, et al. miR-21 overexpression enhances TGF-β1-induced epithelial-to-mesenchymal transition by target smad7 and aggravates renal damage in diabetic nephropathy. Mol Cell Endocrinol. 2014;392:163–172.
   PubMed Web of Science ®Google Scholar
• Nieto MA, Huang R-J, Jackson RA, et al. EMT: 2016. Cell. 2016;166:21–45.
   PubMed Web of Science ®Google Scholar
• Zeisberg M, Duffield JS. Resolved: EMT produces fibroblasts in the kidneyProCon. J Am Soc Nephrol. 2010;21:1247–1253.
   PubMed Web of Science ®Google Scholar
• LeBleu VS, Taduri G, O’Connell J, et al. Origin and function of myofibroblasts in kidney fibrosis. Nat Med. 2013;19:1047–1053.
   PubMed Web of Science ®Google Scholar
• Carew RM, Wang B, Kantharidis P. The role of EMT in renal fibrosis. Cell Tissue Res. 2012;347:103–116.
   PubMed Web of Science ®Google Scholar
• Chang R-M, Xu J-F, Fang F, et al. MicroRNA-130b promotes proliferation and EMT-induced metastasis via PTEN/p-AKT/HIF-1α signaling. Tumor Biol. 2016;37:10609–10619.
   PubMedGoogle Scholar
• Yuan J, Benway CJ, Bagley J, et al. MicroRNA-494 promotes cyclosporine-induced nephrotoxicity and epithelial to mesenchymal transition by inhibiting PTEN: MicroRNAs and cyclosporine nephrotoxicity. Am J Transplant. 2015;15:1682–1691.
   PubMed Web of Science ®Google Scholar
• Xing L, Liu Q, Fu S, et al. PTEN inhibits high glucose-induced phenotypic transition in podocytes: PTEN I NHIBIT P ODOCYTE EMT. J Cell Biochem. 2015;116(8):1776–1784.
   PubMed Web of Science ®Google Scholar
• Bird A. DNA methylation patterns and epigenetic memory. Genes Dev. 2002;16:6–21.
   PubMed Web of Science ®Google Scholar
• Jaenisch R, Bird A. Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet. 2003;33(S3):245–254.
   PubMed Web of Science ®Google Scholar
• Lu Z, Liu N, Wang F. Epigenetic regulations in diabetic nephropathy. J Diabetes Res. 2017;2017:1–6.
   Web of Science ®Google Scholar
• Ko Y-A, Mohtat D, Suzuki M, et al. Cytosine methylation changes in enhancer regions of core pro-fibrotic genes characterize kidney fibrosis development. Genome Biol. 2013;14:R108.
   PubMed Web of Science ®Google Scholar
• Kato M, Dang V, Wang M, et al. TGF- induces acetylation of chromatin and of Ets-1 to alleviate repression of miR-192 in diabetic nephropathy. Sci Signal. 2013;6:ra43–ra43.
   PubMed Web of Science ®Google Scholar
• Bermúdez Brito M. Focus on PTEN regulation. Front Oncol. 2015;5:166.
   PubMed Web of Science ®Google Scholar
• Miranda-Gonçalves V, Lameirinhas A, Henrique R, et al. Metabolism and epigenetic interplay in cancer: regulation and putative therapeutic targets. Front Genet. 2018;9:427.
   PubMed Web of Science ®Google Scholar
• Chen G, Chen H, Ren S, et al. Aberrant DNA methylation of mTOR pathway genes promotes inflammatory activation of immune cells in diabetic kidney disease. Kidney Int. 2019;96:409–420.
   PubMed Web of Science ®Google Scholar
• Yin L, Cai W-J, Chang X-Y, et al. Analysis of PTEN expression and promoter methylation in Uyghur patients with mild type 2 diabetes mellitus. Medicine (Baltimore). 2018;97:e13513.
   PubMedGoogle Scholar
• Barutta F, Bellini S, Mastrocola R, et al. MicroRNA and microvascular complications of diabetes. Int J Endocrinol. 2018;2018:1–20.
   Web of Science ®Google Scholar
• Calin GA, Dumitru CD, Shimizu M, et al. Nonlinear partial differential equations and applications: frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci. 2002;99(24):15524–15529.
   PubMed Web of Science ®Google Scholar
• Calin GA, Ferracin M, Cimmino A, et al. A microRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med. 2005;353:1793–1801.
   PubMed Web of Science ®Google Scholar
• Mitchell PS, Parkin RK, Kroh EM, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci. 2008;105:10513–10518.
   PubMed Web of Science ®Google Scholar
• Lawrie CH, Gal S, Dunlop HM, et al. Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br J Haematol. 2008;141:672–675.
   PubMed Web of Science ®Google Scholar
• Argyropoulos C, Wang K, McClarty S, et al. Urinary microRNA profiling in the nephropathy of type 1 diabetes. PLOS One. 2013;8:e54662.
   PubMed Web of Science ®Google Scholar
• Landgraf P, Rusu M, Sheridan R, et al. A mammalian microRNA expression atlas based on small RNA library sequencing. Cell. 2007;129:1401–1414.
   PubMed Web of Science ®Google Scholar
• Kantharidis P, Wang B, Carew RM, et al. Diabetes complications: the microRNA perspective. Diabetes. 2011;60:1832–1837.
   PubMed Web of Science ®Google Scholar
• Bracken CP, Khew-Goodall Y, Goodall GJ. Network-based approaches to understand the roles of miR-200 and other microRNAs in cancer. Cancer Res. 2015;75:2594–2599.
   PubMed Web of Science ®Google Scholar
• Lin C-L, Lee P-H, Hsu Y-C, et al. MicroRNA-29a promotion of nephrin acetylation ameliorates hyperglycemia-induced podocyte dysfunction. J Am Soc Nephrol. 2014;25:1698–1709.
   PubMed Web of Science ®Google Scholar
• Yu S, Zhao H, Yang W, et al. The alcohol extract of Coreopsis tinctoria nutt ameliorates diabetes and diabetic nephropathy in db/db mice through miR-192/miR-200b and PTEN/AKT and ZEB2/ECM pathways. BioMed Res Int. 2019;2019:1–12.
   Web of Science ®Google Scholar
• Wang Q, Wang Y, Minto AW, et al. MicroRNA-377 is up-regulated and can lead to increased fibronectin production in diabetic nephropathy. Faseb J. 2008;22:4126–4135.
   PubMed Web of Science ®Google Scholar
• Chen Y-Q, Wang X-X, Yao X-M, et al. MicroRNA-195 promotes apoptosis in mouse podocytes via enhanced caspase activity driven by BCL2 insufficiency. Am J Nephrol. 2011;34:549–559.
   PubMed Web of Science ®Google Scholar
• Mu J, Pang Q, Guo Y-H, et al. Functional implications of microRNA-215 in TGF-β1-induced phenotypic transition of mesangial cells by targeting CTNNBIP1. PLOS One. 2013;8:e58622.
   PubMed Web of Science ®Google Scholar
• Alvarez ML, Khosroheidari M, Eddy E, et al. Role of microRNA 1207-5P and its host gene, the long non-coding RNA Pvt1, as mediators of extracellular matrix accumulation in the kidney: implications for diabetic nephropathy. PLOS One. 2013;8(10):e77468.
   PubMed Web of Science ®Google Scholar
• Zhong X, Chung ACK, Chen H-Y, et al. Smad3-mediated upregulation of miR-21 promotes renal fibrosis. J Am Soc Nephrol. 2011;22:1668–1681.
   PubMed Web of Science ®Google Scholar
• Wang Y-Y, Liu R-X, Guo B, et al. [Down-regulation of PTEN expression in kidney and its role in development of diabetic nephropathy in rats]. Sheng Li Xue Bao. 2011;63:325–332.
   PubMedGoogle Scholar
• Godwin JG, Ge X, Stephan K, et al. Identification of a microRNA signature of renal ischemia reperfusion injury. Proc Natl Acad Sci U S A. 2010;107:14339–14344.
   PubMed Web of Science ®Google Scholar
• Lai JY, Luo J, O’Connor C, et al. MicroRNA-21 in glomerular injury. J Am Soc Nephrol. 2015;26:805–816.
   PubMed Web of Science ®Google Scholar
• Dey N, Das F, Mariappan MM, et al. MicroRNA-21 orchestrates high glucose-induced signals to TOR complex 1, resulting in renal cell pathology in diabetes. J Biol Chem. 2011;286:25586–25603.
   PubMed Web of Science ®Google Scholar
• Liu X, Zhang Y, Shi M, et al. Notch1 regulates PTEN expression to exacerbate renal tubulointerstitial fibrosis in diabetic nephropathy by inhibiting autophagy via interactions with Hes1. Biochem Biophys Res Commun. 2018;497:1110–1116.
   PubMed Web of Science ®Google Scholar
• Shen W, Chen G, Dong R, et al. MicroRNA-21/PTEN/Akt axis in the fibrogenesis of biliary atresia. J Pediatr Surg. 2014;49:1738–1741.
   PubMed Web of Science ®Google Scholar
• Chen Z, Yuan Y, Zou X, et al. Radix Puerariae and Fructus crataegi mixture inhibits renal injury in type 2 diabetes via decreasing of AKT/PI3K. BMC Complement Altern Med. 2017;17:454.
   PubMed Web of Science ®Google Scholar
• Birnbaum Y, Nanhwan MK, Ling S, et al. PTEN upregulation may explain the development of insulin resistance and type 2 diabetes with high dose statins. Cardiovasc Drugs Ther. 2014;28:447–457.
   PubMed Web of Science ®Google Scholar
• Henao-Mejia J, Williams A, Goff LA, et al. The microRNA miR-181 is a critical cellular metabolic rheostat essential for NKT cell ontogenesis and lymphocyte development and homeostasis. Immunity. 2013;38:984–997.
   PubMed Web of Science ®Google Scholar
• Wu G, Li G-B, Dai B, et al. The role of microRNAs in diabetic nephropathy. J Diabetes Res. 2014;2014:1–12.
   Web of Science ®Google Scholar
• Wang X, Shen E, Wang Y, et al. Cross talk between miR-214 and PTEN attenuates glomerular hypertrophy under diabetic conditions. Sci Rep. 2016;6:31506.
   PubMed Web of Science ®Google Scholar
• Kato M, Natarajan R. MicroRNAs in diabetic nephropathy: functions, biomarkers, and therapeutic targets: microRNAs in diabetic nephropathy. Ann N Y Acad Sci. 2015;1353:72–88.
   PubMed Web of Science ®Google Scholar
• Dey N, Bera A, Das F, et al. High glucose enhances microRNA-26a to activate mTORC1 for mesangial cell hypertrophy and matrix protein expression. Cell Signal. 2015;27:1276–1285.
   PubMed Web of Science ®Google Scholar
• Li Y, Hu Q, Li C, et al. PTEN-induced partial epithelial-mesenchymal transition drives diabetic kidney disease. J Clin Invest. 2019;129:1129–1151.
   PubMed Web of Science ®Google Scholar
• Wang X, Shen E, Wang Y, et al. Cross talk between miR-214 and PTEN attenuates glomerular hypertrophy under diabetic conditions. Sci Rep. 2016;6:31506..
   PubMed Web of Science ®Google Scholar
• Maity S, Das F, Ghosh‐Choudhury N, et al. High glucose increases miR‐214 to power a feedback loop involving PTEN and the Akt/mTORC1 signaling axis. FEBS Lett. 2019;593:2261–2272.
   PubMed Web of Science ®Google Scholar
• Li X, Wang S, Han Z, et al. Triptolide restores autophagy to alleviate diabetic renal fibrosis through the miR-141-3p/PTEN/Akt/mTOR pathway. Mol Ther-Nucleic Acids. 2017;9:48–56.
   PubMedGoogle Scholar
• Guo L, Tan K, Luo Q, et al. Dihydromyricetin promotes autophagy and attenuates renal interstitial fibrosis by regulating miR-155-5p/PTEN signaling in diabetic nephropathy. Bosn J Basic Med Sci. 2019. [cited 2019 Dec 27]. Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/4410.
   Web of Science ®Google Scholar
• Chen J, Cui Y, Zhang N, et al. Oleanolic acid attenuated diabetic mesangial cell injury by activation of autophagy via miRNA-142-5p/PTEN signaling. Cytotechnology. 2019;71:925–933.
   PubMed Web of Science ®Google Scholar
• Wang Y, He Z, Yang Q, et al. XBP 1 inhibits mesangial cell apoptosis in response to oxidative stress via the PTEN/AKT pathway in diabetic nephropathy. FEBS Open Bio. 2019;9:1249–1258.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Zhao S, Wu D, et al. MicroRNA-22 promotes renal tubulointerstitial fibrosis by targeting PTEN and suppressing autophagy in diabetic nephropathy. J. Diabetes Res. 2018;2018:4728645.
   Web of Science ®Google Scholar
• Wang H, Feng Z, Xie J, et al. Podocyte-specific knockin of PTEN protects kidney from hyperglycemia. Am J Physiol-Ren Physiol. 2018;314:F1096–F1107.
   PubMed Web of Science ®Google Scholar
• Bera A, Das F, Ghosh-Choudhury N, et al. Reciprocal regulation of miR-214 and PTEN by high glucose regulates renal glomerular mesangial and proximal tubular epithelial cell hypertrophy and matrix expansion. Am J Physiol-Cell Physiol. 2017;313:C430–C447.
   PubMed Web of Science ®Google Scholar
• McClelland AD, Herman-Edelstein M, Komers R, et al. miR-21 promotes renal fibrosis in diabetic nephropathy by targeting PTEN and SMAD7. Clin Sci. 2015;129:1237–1249.
   PubMed Web of Science ®Google Scholar
• Bhatt K, Wei Q, Pabla N, et al. MicroRNA-687 induced by hypoxia-inducible factor-1 targets phosphatase and tensin homolog in renal ischemia-reperfusion injury. J Am Soc Nephrol. 2015;26:1588–1596.
   PubMed Web of Science ®Google Scholar
• Kato M, Wang L, Putta S, et al. Post-transcriptional up-regulation of Tsc-22 by Ybx1, a target of miR-216a, mediates TGF-β-induced collagen expression in kidney cells. J Biol Chem. 2010;285:34004–34015.
   PubMed Web of Science ®Google Scholar
• Sun J, Li ZP, Zhang RQ, et al. Repression of miR-217 protects against high glucose-induced podocyte injury and insulin resistance by restoring PTEN-mediated autophagy pathway. Biochem Biophys Res Commun. 2017;483:318–324.
   PubMed Web of Science ®Google Scholar
• Xu G, Ji C, Song G, et al. MiR-26b modulates insulin sensitivity in adipocytes by interrupting the PTEN/PI3K/AKT pathway. Int J Obes. 2015;39:1523–1530.
   Web of Science ®Google Scholar