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A Glimpse of the Mechanisms Related to Renal Fibrosis in Diabetic Nephropathy

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Renal Fibrosis: Mechanisms and Therapies

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1165))

Abstract

Diabetic nephropathy (DN) is a common kidney disease in people with diabetes, which is also a serious microvascular complication of diabetes and the main cause of end-stage renal disease (ESRD) in developed and developing countries. Renal fibrosis is a finally pathological change in DN. Nevertheless, the relevant mechanism of cause to renal fibrosis in DN is still complex. In this review, we summarized that the role of cell growth factors, epithelial–mesenchymal transition (EMT) in the renal fibrosis of DN, we also highlighted the miRNA and inflammatory cells, such as macrophage, T lymphocyte, and mastocyte modulate the progression of DN. In addition, there are certain other mechanisms that may yet be conclusively defined. Recent studies demonstrated that some of the new signaling pathways or molecules, such as Notch, Wnt, mTOR, Epac-Rap-1 pathway, may play a pivotal role in the modulation of ECM accumulation and renal fibrosis in DN. This review aims to elucidate the mechanism of renal fibrosis in DN and has provided new insights into possible therapeutic interventions to inhibit renal fibrosis and delay the development of DN.

Ling-Feng Zeng and Ying Xiao contributed equally to this work.

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References

  • Adler SG, Schwartz S, Williams ME, Arauz-Pacheco C, Bolton WK, Lee T et al (2010) Phase 1 study of anti-CTGF monoclonal antibody in patients with diabetes and microalbuminuria. Clin J Am Soc Nephrol 5:1420–1428

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Aggarwal N, Kare PK, Varshney P, Kalra OP, Madhu SV, Banerjee BD et al (2017) Role of angiotensin converting enzyme and angiotensinogen gene polymorphisms in angiotensin converting enzyme inhibitor-mediated antiproteinuric action in type 2 diabetic nephropathy patients. World J Diabetes 8:112–119

    Article  PubMed  PubMed Central  Google Scholar 

  • Aghadavod E, Khodadadi S, Baradaran A, Nasri P, Bahmani M, Rafieian-Kopaei M (2016) Role of oxidative stress and inflammatory factors in diabetic kidney disease. Iran J Kidney Dis 10:337–343

    PubMed  Google Scholar 

  • Assmann TS, Recamonde-Mendoza M, de Souza BM, Bauer AC, Crispim D (2018) MicroRNAs and diabetic kidney disease: systematic review and bioinformatic analysis. Mol Cell Endocrinol 477:90–102

    Article  CAS  PubMed  Google Scholar 

  • Balakumar P, Reddy J, Singh M (2009) Do resident renal mast cells play a role in the pathogenesis of diabetic nephropathy? Mol Cell Biochem 330:187–192

    Article  CAS  PubMed  Google Scholar 

  • Bao NN, Kong DY, Zhu D, Hao LR (2015) Influence of overexpression of SOCS2 on cells of DN rat. Asian Pac J Trop Med 8:583–589

    Article  CAS  PubMed  Google Scholar 

  • Bedogni B (2014) Notch signaling in melanoma: interacting pathways and stromal influences that enhance Notch targeting. Pigment Cell Melanoma Res 27:162–168

    Article  CAS  PubMed  Google Scholar 

  • Bending JJ, Lobo-Yeo A, Vergani D, Viberti GC (1988) Proteinuria and activated T-lymphocytes in diabetic nephropathy. Diabetes 37:507–511

    Article  CAS  PubMed  Google Scholar 

  • Ben-Shushan E, Feldman E, Reubinoff BE (2015) Notch signaling regulates motor neuron differentiation of human embryonic stem cells. Stem Cells 33:403–415

    Article  CAS  PubMed  Google Scholar 

  • Benz K, Amann K (2011) Endothelin in diabetic renal disease. Contrib Nephrol 172:139–148

    Article  CAS  PubMed  Google Scholar 

  • Bos JL (2003) Epac: a new cAMP target and new avenues in cAMP research. Nat Rev Mol Cell Biol 4:733–738

    Article  CAS  PubMed  Google Scholar 

  • Bracken CP, Khew-Goodall Y, Goodall GJ (2015) Network-based approaches to understand the roles of miR-200 and other microRNAs in cancer. Cancer Res 75:2594–2599

    Article  CAS  PubMed  Google Scholar 

  • Brosius FC, Tuttle KR, Kretzler M (2016) JAK inhibition in the treatment of diabetic kidney disease. Diabetologia 59:1624–1627

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bruserud O, Pawelec G (1997) Interleukin-13 secretion by normal and posttransplant T lymphocytes; in vitro studies of cellular immune responses in the presence of acute leukaemia blast cells. Cancer Immunol Immunother 45:45–52

    Article  CAS  PubMed  Google Scholar 

  • Burotto M, Chiou VL, Lee JM, Kohn EC (2014) The MAPK pathway across different malignancies: a new perspective. Cancer 120:3446–3456

    Article  CAS  PubMed  Google Scholar 

  • Cai B, Cai JP, Luo YL, Chen C, Zhang S (2015) The specific roles of JAK/STAT signaling pathway in sepsis. Inflammation 38:1599–1608

    Article  CAS  PubMed  Google Scholar 

  • Chandrasekaran K, Karolina DS, Sepramaniam S, Armugam A, Wintour EM, Bertram JF et al (2012) Role of microRNAs in kidney homeostasis and disease. Kidney Int 81:617–627

    Article  CAS  PubMed  Google Scholar 

  • Chau BN, Xin C, Hartner J, Ren S, Castano AP, Linn G et al (2012) MicroRNA-21 promotes fibrosis of the kidney by silencing metabolic pathways. Sci Transl Med 4:118r–121r

    Article  CAS  Google Scholar 

  • Chen HY, Zhong X, Huang XR, Meng XM, You Y, Chung AC et al (2014) MicroRNA-29b inhibits diabetic nephropathy in db/db mice. Mol Ther 22:842–853

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Chen H, Yang X, Lu K, Lu C, Zhao Y, Zheng S et al (2017) Inhibition of high glucose-induced inflammation and fibrosis by a novel curcumin derivative prevents renal and heart injury in diabetic mice. Toxicol Lett 278:48–58

    Article  CAS  PubMed  Google Scholar 

  • Cheng M, Liu F, Peng Y, Chen J, Chen G, Xiao L et al (2014) Construction of a CTGF and RFP-coexpressed renal tubular epithelial cell and its application on evaluation of CTGF-specific siRNAs on epithelial-mesenchymal transition. Urology 83:1441–1443

    Article  Google Scholar 

  • Cheng M, Liu H, Zhang D, Liu Y, Wang C, Liu F et al (2015) HMGB1 enhances the AGE-induced expression of CTGF and TGF-beta via RAGE-dependent signaling in renal tubular epithelial cells. Am J Nephrol 41:257–266

    Article  CAS  PubMed  Google Scholar 

  • Chuang PY, He JC (2010) JAK/STAT signaling in renal diseases. Kidney Int 78:231–234

    Article  CAS  PubMed  Google Scholar 

  • Chung AC, Huang XR, Meng X, Lan HY (2010) miR-192 mediates TGF-beta/Smad3-driven renal fibrosis. J Am Soc Nephrol 21:1317–1325

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chung AC, Dong Y, Yang W, Zhong X, Li R, Lan HY (2013) Smad7 suppresses renal fibrosis via altering expression of TGF-beta/Smad3-regulated microRNAs. Mol Ther 21:388–398

    Article  CAS  PubMed  Google Scholar 

  • Crean JK, Furlong F, Mitchell D, McArdle E, Godson C, Martin F (2006) Connective tissue growth factor/CCN2 stimulates actin disassembly through Akt/protein kinase B-mediated phosphorylation and cytoplasmic translocation of p27(Kip-1). FASEB J 20:1712–1714

    Article  CAS  PubMed  Google Scholar 

  • Danilewicz M, Wagrowska-Danilewicz M (2005) Immunohistochemical analysis of the interstitial mast cells in rebiopsied patients with idiopathic mesangial proliferative glomerulonephritis. Pol J Pathol 56:63–68

    PubMed  Google Scholar 

  • Davis RJ (1994) MAPKs: new JNK expands the group. Trends Biochem Sci 19:470–473

    Article  CAS  PubMed  Google Scholar 

  • de Borst MH, Prakash J, Sandovici M, Klok PA, Hamming I, Kok RJ et al (2009) c-Jun NH2-terminal kinase is crucially involved in renal tubulo-interstitial inflammation. J Pharmacol Exp Ther 331:896–905

    Article  PubMed  CAS  Google Scholar 

  • de Larco JE, Todaro GJ (1980) Sarcoma growth factor (SGF): specific binding to epidermal growth factor (EGF) membrane receptors. J Cell Physiol 102:267–277

    Article  PubMed  Google Scholar 

  • de Rooij J, Zwartkruis FJ, Verheijen MH, Cool RH, Nijman SM, Wittinghofer A et al (1998) Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP. Nature 396:474–477

    Article  PubMed  CAS  Google Scholar 

  • Deshpande SD, Putta S, Wang M, Lai JY, Bitzer M, Nelson RG et al (2013) Transforming growth factor-beta-induced cross talk between p53 and a microRNA in the pathogenesis of diabetic nephropathy. Diabetes 62:3151–3162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Donate-Correa J, Martin-Nunez E, Muros-de-Fuentes M, Mora-Fernandez C, Navarro-Gonzalez JF (2015) Inflammatory cytokines in diabetic nephropathy. J Diabetes Res 2015:948417

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Dounousi E, Duni A, Leivaditis K, Vaios V, Eleftheriadis T, Liakopoulos V (2015) Improvements in the management of diabetic nephropathy. Rev Diabet Stud 12:119–133

    Article  PubMed  PubMed Central  Google Scholar 

  • Egido J, Rojas-Rivera J, Mas S, Ruiz-Ortega M, Sanz AB, Gonzalez PE et al (2017) Atrasentan for the treatment of diabetic nephropathy. Expert Opin Invest Drugs 26:741–750

    Article  CAS  Google Scholar 

  • Esposito C, Fasoli G, Rampino T, Dal Canton A (2006) Hepatocyte growth factor and kidney. G Ital Nefrol 23:381–388

    CAS  PubMed  Google Scholar 

  • Feng M, Tang PM, Huang XR, Sun SF, You YK, Xiao J et al (2018) TGF-beta Mediates renal fibrosis via the Smad3-Erbb4-IR long noncoding RNA axis. Mol Ther 26:148–161

    Article  CAS  PubMed  Google Scholar 

  • Fukasawa H, Yamamoto T, Suzuki H, Togawa A, Ohashi N, Fujigaki Y et al (2004) Treatment with anti-TGF-beta antibody ameliorates chronic progressive nephritis by inhibiting Smad/TGF-beta signaling. Kidney Int 65:63–74

    Article  CAS  PubMed  Google Scholar 

  • Gao Q, Shen W, Qin W, Zheng C, Zhang M, Zeng C et al (2010) Treatment of db/db diabetic mice with triptolide: a novel therapy for diabetic nephropathy. Nephrol Dial Transplant 25:3539–3547

    Article  CAS  PubMed  Google Scholar 

  • Glowacki F, Savary G, Gnemmi V, Buob D, Van der Hauwaert C, Lo-Guidice JM et al (2013) Increased circulating miR-21 levels are associated with kidney fibrosis. PLoS ONE 8:e58014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gohda E (2002) Function and regulation of production of hepatocyte growth factor (HGF). Nihon Yakurigaku Zasshi 119:287–294

    Article  CAS  PubMed  Google Scholar 

  • Goto E, Honjo S, Yamashita H, Shomori K, Adachi H, Ito H (2002) Mast cells in human allografted kidney: correlation with interstitial fibrosis. Clin Transplant 16(Suppl 8):7–11

    Article  PubMed  Google Scholar 

  • Guha M, Xu ZG, Tung D, Lanting L, Natarajan R (2007) Specific down-regulation of connective tissue growth factor attenuates progression of nephropathy in mouse models of type 1 and type 2 diabetes. FASEB J 21:3355–3368

    Article  CAS  PubMed  Google Scholar 

  • Hathaway CK, Gasim AM, Grant R, Chang AS, Kim HS, Madden VJ et al (2015) Low TGFbeta1 expression prevents and high expression exacerbates diabetic nephropathy in mice. Proc Natl Acad Sci U S A 112:5815–5820

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hay ED, Zuk A (1995) Transformations between epithelium and mesenchyme: normal, pathological, and experimentally induced. Am J Kidney Dis 26:678–690

    Article  CAS  PubMed  Google Scholar 

  • He J, Yuan G, Cheng F, Zhang J, Guo X (2017) Mast cell and M1 macrophage infiltration and local pro-inflammatory factors were attenuated with incretin-based therapies in obesity-related glomerulopathy. Metab Syndr Relat Disord 15:344–353

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hickey FB, Martin F (2018) Role of the immune system in diabetic kidney disease. Curr Diab Rep 18:20

    Article  PubMed  CAS  Google Scholar 

  • Ho C, Lee PH, Hsu YC, Wang FS, Huang YT, Lin CL (2012) Sustained Wnt/beta-catenin signaling rescues high glucose induction of transforming growth factor-beta1-mediated renal fibrosis. Am J Med Sci 344:374–382

    Article  PubMed  Google Scholar 

  • Hong JP, Li XM, Li MX, Zheng FL (2013) VEGF suppresses epithelial-mesenchymal transition by inhibiting the expression of Smad3 and miR192, a Smad3-dependent microRNA. Int J Mol Med 31:1436–1442

    Article  CAS  PubMed  Google Scholar 

  • Hou M, Bao X, Luo F, Chen X, Liu L, Wu M (2018) HMGA2 modulates the TGFbeta/Smad, TGFbeta/ERK and Notch signaling pathways in human lens epithelial-mesenchymal transition. Curr Mol Med 18:71–82

    Article  CAS  PubMed  Google Scholar 

  • Hu HH, Chen DQ, Wang YN, Feng YL, Cao G, Vaziri ND et al (2018) New insights into TGF-beta/smad signaling in tissue fibrosis. Chem Biol Interact 292:76–83

    Article  CAS  PubMed  Google Scholar 

  • Huang JS, Guh JY, Chen HC, Hung WC, Lai YH, Chuang LY (2001) Role of receptor for advanced glycation end-product (RAGE) and the JAK/STAT-signaling pathway in AGE-induced collagen production in NRK-49F cells. J Cell Biochem 81:102–113

    Article  CAS  PubMed  Google Scholar 

  • Huang S, Liu F, Niu Q, Li Y, Liu C, Zhang L et al (2013) GLIPR-2 overexpression in HK-2 cells promotes cell EMT and migration through ERK1/2 activation. PLoS ONE 8:e58574

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang Y, Tong J, He F, Yu X, Fan L, Hu J et al (2015) miR-141 regulates TGF-beta1-induced epithelial-mesenchymal transition through repression of HIPK2 expression in renal tubular epithelial cells. Int J Mol Med 35:311–318

    Article  CAS  PubMed  Google Scholar 

  • Hwang I, Seo EY, Ha H (2009) Wnt/beta-catenin signaling: a novel target for therapeutic intervention of fibrotic kidney disease. Arch Pharm Res 32:1653–1662

    Article  CAS  PubMed  Google Scholar 

  • Jafari M, Ghadami E, Dadkhah T, Akhavan-Niaki H (2019) PI3k/AKT signaling pathway: erythropoiesis and beyond. J Cell Physiol 234:2373–2385

    Article  CAS  PubMed  Google Scholar 

  • Jang YN, Baik EJ (2013) JAK-STAT pathway and myogenic differentiation. JAKSTAT 2:e23282

    PubMed  PubMed Central  Google Scholar 

  • Jenkins RH, Martin J, Phillips AO, Bowen T, Fraser DJ (2012a) Pleiotropy of microRNA-192 in the kidney. Biochem Soc Trans 40:762–767

    Article  CAS  PubMed  Google Scholar 

  • Jenkins RH, Martin J, Phillips AO, Bowen T, Fraser DJ (2012b) Transforming growth factor beta1 represses proximal tubular cell microRNA-192 expression through decreased hepatocyte nuclear factor DNA binding. Biochem J 443:407–416

    Article  CAS  PubMed  Google Scholar 

  • Jiang L, Qiu W, Zhou Y, Wen P, Fang L, Cao H et al (2013) A microRNA-30e/mitochondrial uncoupling protein 2 axis mediates TGF-beta1-induced tubular epithelial cell extracellular matrix production and kidney fibrosis. Kidney Int 84:285–296

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Juan YS, Chuang SM, Long CY, Lin RJ, Liu KM, Wu WJ et al (2012) Protein kinase C inhibitor prevents renal apoptotic and fibrotic changes in response to partial ureteric obstruction. BJU Int 110:283–292

    Article  CAS  PubMed  Google Scholar 

  • Kanasaki K, Shi S, Kanasaki M, He J, Nagai T, Nakamura Y et al (2014) Linagliptin-mediated DPP-4 inhibition ameliorates kidney fibrosis in streptozotocin-induced diabetic mice by inhibiting endothelial-to-mesenchymal transition in a therapeutic regimen. Diabetes 63:2120–2131

    Article  CAS  PubMed  Google Scholar 

  • Kang MJ, Wu X, Ly H, Thai K, Scholey JW (1999) Effect of glucose on stress-activated protein kinase activity in mesangial cells and diabetic glomeruli. Kidney Int 55:2203–2214

    Article  CAS  PubMed  Google Scholar 

  • Kanwar YS, Sun L, Xie P, Liu FY, Chen S (2011) A glimpse of various pathogenetic mechanisms of diabetic nephropathy. Annu Rev Pathol 6:395–423

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kato M, Natarajan R (2014) Diabetic nephropathy—emerging epigenetic mechanisms. Nat Rev Nephrol 10:517–530

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kato M, Natarajan R (2015) MicroRNAs in diabetic nephropathy: functions, biomarkers, and therapeutic targets. Ann N Y Acad Sci 1353:72–88

    Article  PubMed  PubMed Central  Google Scholar 

  • Kato M, Zhang J, Wang M, Lanting L, Yuan H, Rossi JJ et al (2007) MicroRNA-192 in diabetic kidney glomeruli and its function in TGF-beta-induced collagen expression via inhibition of E-box repressors. Proc Natl Acad Sci U S A 104:3432–3437

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kato M, Arce L, Wang M, Putta S, Lanting L, Natarajan R (2011) A microRNA circuit mediates transforming growth factor-beta1 autoregulation in renal glomerular mesangial cells. Kidney Int 80:358–368

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kato M, Dang V, Wang M, Park JT, Deshpande S, Kadam S et al (2013) TGF-beta induces acetylation of chromatin and of Ets-1 to alleviate repression of miR-192 in diabetic nephropathy. Sci Signal 6:a43

    Article  CAS  Google Scholar 

  • Kim SM, Lee SH, Lee A, Kim DJ, Kim YG, Kim SY et al (2015) Targeting T helper 17 by mycophenolate mofetil attenuates diabetic nephropathy progression. Transl Res 166:375–383

    Article  CAS  PubMed  Google Scholar 

  • Kinashi H, Falke LL, Nguyen TQ, Bovenschen N, Aten J, Leask A et al (2017) Connective tissue growth factor regulates fibrosis-associated renal lymphangiogenesis. Kidney Int 92:850–863

    Article  CAS  PubMed  Google Scholar 

  • Kolling M, Kaucsar T, Schauerte C, Hubner A, Dettling A, Park JK et al (2017) Therapeutic miR-21 silencing ameliorates diabetic kidney disease in mice. Mol Ther 25:165–180

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kopan R, Ilagan MX (2009) The canonical Notch signaling pathway: unfolding the activation mechanism. Cell 137:216–233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Krupa A, Jenkins R, Luo DD, Lewis A, Phillips A, Fraser D (2010) Loss of MicroRNA-192 promotes fibrogenesis in diabetic nephropathy. J Am Soc Nephrol 21:438–447

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lai JY, Luo J, O’Connor C, Jing X, Nair V, Ju W et al (2015) MicroRNA-21 in glomerular injury. J Am Soc Nephrol 26:805–816

    Article  CAS  PubMed  Google Scholar 

  • Lan X, Wen H, Aslam R, Shoshtari S, Mishra A, Kumar V et al (2018) Nicotine enhances mesangial cell proliferation and fibronectin production in high glucose milieu via activation of Wnt/beta-catenin pathway. Biosci Rep 38

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee RC, Feinbaum RL, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75:843–854

    Article  CAS  PubMed  Google Scholar 

  • Li J, Bertram JF (2010) Review: endothelial-myofibroblast transition, a new player in diabetic renal fibrosis. Nephrology (Carlton) 15:507–512

    Article  Google Scholar 

  • Liau N, Laktyushin A, Lucet IS, Murphy JM, Yao S, Whitlock E et al (2018) The molecular basis of JAK/STAT inhibition by SOCS1. Nat Commun 9:1558

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Libetta C, Esposito P, Martinelli C, Grosjean F, Gregorini M, Rampino T et al (2016) Hepatocyte growth factor (HGF) and hemodialysis: physiopathology and clinical implications. Clin Exp Nephrol 20:371–378

    Article  CAS  PubMed  Google Scholar 

  • Lim AK, Tesch GH (2012) Inflammation in diabetic nephropathy. Mediat Inflamm 2012:146154

    Article  CAS  Google Scholar 

  • Lin S, Sahai A, Chugh SS, Pan X, Wallner EI, Danesh FR et al (2002) High glucose stimulates synthesis of fibronectin via a novel protein kinase C, Rap1b, and B-Raf signaling pathway. J Biol Chem 277:41725–41735

    Article  CAS  PubMed  Google Scholar 

  • Lin CL, Wang FS, Hsu YC, Chen CN, Tseng MJ, Saleem MA et al (2010a) Modulation of notch-1 signaling alleviates vascular endothelial growth factor-mediated diabetic nephropathy. Diabetes 59:1915–1925

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin CL, Wang JY, Ko JY, Huang YT, Kuo YH, Wang FS (2010b) Dickkopf-1 promotes hyperglycemia-induced accumulation of mesangial matrix and renal dysfunction. J Am Soc Nephrol 21:124–135

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin CL, Lee PH, Hsu YC, Lei CC, Ko JY, Chuang PC et al (2014) MicroRNA-29a promotion of nephrin acetylation ameliorates hyperglycemia-induced podocyte dysfunction. J Am Soc Nephrol 25:1698–1709

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin Y, Zhao JL, Zheng QJ, Jiang X, Tian J, Liang SQ et al (2018) Notch signaling modulates macrophage polarization and phagocytosis through direct suppression of signal regulatory protein alpha expression. Front Immunol 9:1744

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Liu Y (2010) New insights into epithelial-mesenchymal transition in kidney fibrosis. J Am Soc Nephrol 21:212–222

    Article  CAS  PubMed  Google Scholar 

  • Liu Q, Xing L, Wang L, Yao F, Liu S, Hao J et al (2014a) Therapeutic effects of suppressors of cytokine signaling in diabetic nephropathy. J Histochem Cytochem 62:119–128

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Liu R, Zhong Y, Li X, Chen H, Jim B, Zhou MM et al (2014b) Role of transcription factor acetylation in diabetic kidney disease. Diabetes 63:2440–2453

    Article  PubMed  PubMed Central  Google Scholar 

  • Liu H, Wang X, Liu S, Li H, Yuan X, Feng B et al (2016a) Effects and mechanism of miR-23b on glucose-mediated epithelial-to-mesenchymal transition in diabetic nephropathy. Int J Biochem Cell Biol 70:149–160

    Article  CAS  PubMed  Google Scholar 

  • Liu XJ, Hong Q, Wang Z, Yu YY, Zou X, Xu LH (2016b) MicroRNA21 promotes interstitial fibrosis via targeting DDAH1: a potential role in renal fibrosis. Mol Cell Biochem 411:181–189

    Article  CAS  PubMed  Google Scholar 

  • Liu D, Cao Y, Zhang X, Peng C, Tian X, Yan C et al (2018) Chemokine CC-motif ligand 2 participates in platelet function and arterial thrombosis by regulating PKCalpha-P38MAPK-HSP27 pathway. Biochim Biophys Acta 1864:2901–2912

    Article  CAS  Google Scholar 

  • Loeffler I, Wolf G (2015) Epithelial-to-mesenchymal transition in diabetic nephropathy: fact or fiction? Cells 4:631–652

    Article  PubMed  PubMed Central  Google Scholar 

  • Long J, Wang Y, Wang W, Chang BH, Danesh FR (2011) MicroRNA-29c is a signature microRNA under high glucose conditions that targets Sprouty homolog 1, and its in vivo knockdown prevents progression of diabetic nephropathy. J Biol Chem 286:11837–11848

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lopez-Arribillaga E, Rodilla V, Colomer C, Vert A, Shelton A, Cheng JH et al (2018) Manic Fringe deficiency imposes Jagged1 addiction to intestinal tumor cells. Nat Commun 9:2992

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lu Q, Zuo WZ, Ji XJ, Zhou YX, Liu YQ, Yao XQ et al (2015) Ethanolic Ginkgo biloba leaf extract prevents renal fibrosis through Akt/mTOR signaling in diabetic nephropathy. Phytomedicine 22:1071–1078

    Article  CAS  PubMed  Google Scholar 

  • Lv LL, Liu BC (2015) Role of non-classical renin-angiotensin system axis in renal fibrosis. Front Physiol 6:117

    Article  PubMed  PubMed Central  Google Scholar 

  • Manson SR, Austin PF, Guo Q, Moore KH (2015) BMP-7 signaling and its critical roles in kidney development, the responses to renal injury, and chronic kidney disease. Vitam Horm 99:91–144

    Article  CAS  PubMed  Google Scholar 

  • March JT, Golshirazi G, Cernisova V, Carr H, Leong Y, Lu-Nguyen N et al (2018) Targeting TGFbeta signaling to address fibrosis using antisense oligonucleotides. Biomedicines 6

    Google Scholar 

  • Mariappan MM, Shetty M, Sataranatarajan K, Choudhury GG, Kasinath BS (2008) Glycogen synthase kinase 3beta is a novel regulator of high glucose- and high insulin-induced extracellular matrix protein synthesis in renal proximal tubular epithelial cells. J Biol Chem 283:30566–30575

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mason RM (2009) Connective tissue growth factor (CCN2), a pathogenic factor in diabetic nephropathy. What does it do? How does it do it? J Cell Commun Signal 3:95–104

    Article  PubMed  PubMed Central  Google Scholar 

  • McClelland AD, Herman-Edelstein M, Komers R, Jha JC, Winbanks CE, Hagiwara S et al (2015) miR-21 promotes renal fibrosis in diabetic nephropathy by targeting PTEN and SMAD7. Clin Sci (Lond) 129:1237–1249

    Article  CAS  Google Scholar 

  • Meng XM, Huang XR, Xiao J, Chen HY, Zhong X, Chung AC et al (2012) Diverse roles of TGF-beta receptor II in renal fibrosis and inflammation in vivo and in vitro. J Pathol 227:175–188

    Article  CAS  PubMed  Google Scholar 

  • Meng X, Chung ACK, Lan HY (2013) Role of the TGF-β/BMP-7/Smad pathways in renal diseases. Clin Sci 124:243–254

    Article  CAS  Google Scholar 

  • Meng XM, Tang PM, Li J, Lan HY (2015) TGF-beta/Smad signaling in renal fibrosis. Front Physiol 6:82

    Article  PubMed  PubMed Central  Google Scholar 

  • Meng XM, Nikolic-Paterson DJ, Lan HY (2016) TGF-beta: the master regulator of fibrosis. Nat Rev Nephrol 12:325–338

    Article  CAS  PubMed  Google Scholar 

  • Menne J, Shushakova N, Bartels J, Kiyan Y, Laudeley R, Haller H et al (2013) Dual inhibition of classical protein kinase C-alpha and protein kinase C-beta isoforms protects against experimental murine diabetic nephropathy. Diabetes 62:1167–1174

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mizuno S, Nakamura T (2004) Suppressions of chronic glomerular injuries and TGF-beta 1 production by HGF in attenuation of murine diabetic nephropathy. Am J Physiol Renal Physiol 286:F134–F143

    Article  CAS  PubMed  Google Scholar 

  • Mizuno S, Matsumoto K, Nakamura T (2008) HGF as a renotrophic and anti-fibrotic regulator in chronic renal disease. Front Biosci 13:7072–7086

    Article  CAS  PubMed  Google Scholar 

  • Mohamed R, Jayakumar C, Chen F, Fulton D, Stepp D, Gansevoort RT et al (2016) Low-dose IL-17 therapy prevents and reverses diabetic nephropathy, metabolic syndrome, and associated organ fibrosis. J Am Soc Nephrol 27:745–765

    Article  CAS  PubMed  Google Scholar 

  • Moon JY, Jeong KH, Lee TW, Ihm CG, Lim SJ, Lee SH (2012) Aberrant recruitment and activation of T cells in diabetic nephropathy. Am J Nephrol 35:164–174

    Article  CAS  PubMed  Google Scholar 

  • Moriya R, Manivel JC, Mauer M (2004) Juxtaglomerular apparatus T-cell infiltration affects glomerular structure in Type 1 diabetic patients. Diabetologia 47:82–88

    Article  CAS  PubMed  Google Scholar 

  • Mou X, Zhou DY, Zhou DY, Ma JR, Liu YH, Chen HP et al (2016) Serum TGF-beta1 as a biomarker for type 2 diabetic nephropathy: a meta-analysis of randomized controlled trials. PLoS ONE 11:e149513

    Google Scholar 

  • Mu J, Pang Q, Guo YH, Chen JG, Zeng W, Huang YJ et al (2013) Functional implications of microRNA-215 in TGF-beta1-induced phenotypic transition of mesangial cells by targeting CTNNBIP1. PLoS ONE 8:e58622

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Natarajan R, Putta S, Kato M (2012) MicroRNAs and diabetic complications. J Cardiovasc Transl Res 5:413–422

    Article  PubMed  PubMed Central  Google Scholar 

  • Navarro-Gonzalez JF, Mora-Fernandez C, Muros DFM, Garcia-Perez J (2011) Inflammatory molecules and pathways in the pathogenesis of diabetic nephropathy. Nat Rev Nephrol 7:327–340

    Article  CAS  PubMed  Google Scholar 

  • Nguyen TQ, Roestenberg P, van Nieuwenhoven FA, Bovenschen N, Li Z, Xu L et al (2008) CTGF inhibits BMP-7 signaling in diabetic nephropathy. J Am Soc Nephrol 19:2098–2107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nlandu KS, Neelisetty S, Woodbury L, Green E, Harris RC, Zent R (2016) Deleting the TGF-beta receptor in proximal tubules impairs HGF signaling. Am J Physiol Renal Physiol 310:F499–F510

    Article  CAS  Google Scholar 

  • Noetel A, Kwiecinski M, Elfimova N, Huang J, Odenthal M (2012) microRNA are central players in anti- and profibrotic gene regulation during liver fibrosis. Front Physiol 3:49

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oba S, Kumano S, Suzuki E, Nishimatsu H, Takahashi M, Takamori H et al (2010) miR-200b precursor can ameliorate renal tubulointerstitial fibrosis. PLoS ONE 5:e13614

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ohta M, Chosa N, Kyakumoto S, Yokota S, Okubo N, Nemoto A et al (2018) IL-1β and TNF-α suppress TGF-β-promoted NGF expression in periodontal ligament-derived fibroblasts through inactivation of TGF-β- induced Smad2/3- and p38 MAPK-mediated signals. Int J Mol Med 42:1484–1494

    CAS  PubMed  PubMed Central  Google Scholar 

  • Okada S, Shikata K, Matsuda M, Ogawa D, Usui H, Kido Y et al (2003) Intercellular adhesion molecule-1-deficient mice are resistant against renal injury after induction of diabetes. Diabetes 52:2586–2593

    Article  CAS  PubMed  Google Scholar 

  • Okayama Y, Kawakami T (2006) Development, migration, and survival of mast cells. Immunol Res 34:97–115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oldfield MD, Bach LA, Forbes JM, Nikolic-Paterson D, McRobert A, Thallas V et al (2001) Advanced glycation end products cause epithelial-myofibroblast transdifferentiation via the receptor for advanced glycation end products (RAGE). J Clin Invest 108:1853–1863

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pan J, Zhang J, Zhang X, Zhou X, Lu S, Huang X et al (2014) Role of microRNA-29b in angiotensin II-induced epithelial-mesenchymal transition in renal tubular epithelial cells. Int J Mol Med 34:1381–1387

    Article  CAS  PubMed  Google Scholar 

  • Park JT, Kato M, Yuan H, Castro N, Lanting L, Wang M et al (2013) FOG2 protein down-regulation by transforming growth factor-beta1-induced microRNA-200b/c leads to Akt kinase activation and glomerular mesangial hypertrophy related to diabetic nephropathy. J Biol Chem 288:22469–22480

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Peng R, Zhou L, Zhou Y, Zhao Y, Li Q, Ni D et al (2015) MiR-30a inhibits the epithelial-mesenchymal transition of podocytes through downregulation of NFATc3. Int J Mol Sci 16:24032–24047

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Putta S, Lanting L, Sun G, Lawson G, Kato M, Natarajan R (2012) Inhibiting microRNA-192 ameliorates renal fibrosis in diabetic nephropathy. J Am Soc Nephrol 23:458–469

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rahimi Z (2016) The role of renin angiotensin aldosterone system genes in diabetic nephropathy. Can J Diabetes 40:178–183

    Article  PubMed  Google Scholar 

  • Rane MJ, Song Y, Jin S, Barati MT, Wu R, Kausar H et al (2010) Interplay between Akt and p38 MAPK pathways in the regulation of renal tubular cell apoptosis associated with diabetic nephropathy. Am J Physiol Renal Physiol 298:F49–F61

    Article  CAS  PubMed  Google Scholar 

  • Reddy MA, Tak PJ, Natarajan R (2013) Epigenetic modifications in the pathogenesis of diabetic nephropathy. Semin Nephrol 33:341–353

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rousselle A, Kettritz R, Schreiber A (2017) Monocytes promote crescent formation in anti-myeloperoxidase antibody-induced glomerulonephritis. Am J Pathol 187:1908–1915

    Article  CAS  PubMed  Google Scholar 

  • Sanai T, Sobka T, Johnson T, El-Essawy M, Muchaneta-Kubara EC, Ben GO et al (2000) Expression of cytoskeletal proteins during the course of experimental diabetic nephropathy. Diabetologia 43:91–100

    Article  CAS  PubMed  Google Scholar 

  • Shemesh II, Rozen-Zvi B, Kalechman Y, Gafter U, Sredni B (2014) AS101 prevents diabetic nephropathy progression and mesangial cell dysfunction: regulation of the AKT downstream pathway. PLoS ONE 9:e114287

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Shi S, Yu L, Chiu C, Sun Y, Chen J, Khitrov G et al (2008) Podocyte-selective deletion of dicer induces proteinuria and glomerulosclerosis. J Am Soc Nephrol 19:2159–2169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Simpson K, Wonnacott A, Fraser DJ, Bowen T (2016) MicroRNAs in diabetic nephropathy: from biomarkers to therapy. Curr Diab Rep 16:35

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Singh M, Yelle N, Venugopal C, Singh SK (2018) EMT: mechanisms and therapeutic implications. Pharmacol Ther 182:80–94

    Article  CAS  PubMed  Google Scholar 

  • Sirin Y, Susztak K (2012) Notch in the kidney: development and disease. J Pathol 226:394–403

    Article  CAS  PubMed  Google Scholar 

  • Sun L, Kondeti VK, Xie P, Raparia K, Kanwar YS (2011a) Epac1-mediated, high glucose-induced renal proximal tubular cells hypertrophy via the Akt/p21 pathway. Am J Pathol 179:1706–1718

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sun L, Zhang D, Liu F, Xiang X, Ling G, Xiao L et al (2011b) Low-dose paclitaxel ameliorates fibrosis in the remnant kidney model by down-regulating miR-192. J Pathol 225:364–377

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Teng B, Duong M, Tossidou I, Yu X, Schiffer M (2014) Role of protein kinase C in podocytes and development of glomerular damage in diabetic nephropathy. Front Endocrinol (Lausanne) 5:179

    Article  Google Scholar 

  • Tesch GH (2017) Diabetic nephropathy—is this an immune disorder? Clin Sci (Lond) 131:2183–2199

    Article  CAS  Google Scholar 

  • Togawa H, Nakanishi K, Shima Y, Obana M, Sako M, Nozu K et al (2009) Increased chymase-positive mast cells in children with crescentic glomerulonephritis. Pediatr Nephrol 24:1071–1075

    Article  PubMed  Google Scholar 

  • Trionfini P, Benigni A (2017) MicroRNAs as master regulators of glomerular function in health and disease. J Am Soc Nephrol 28:1686–1696

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Trionfini P, Benigni A, Remuzzi G (2015) MicroRNAs in kidney physiology and disease. Nat Rev Nephrol 11:23–33

    Article  CAS  PubMed  Google Scholar 

  • Tripurani SK, Wang Y, Fan YX, Rahimi M, Wong L, Lee MH et al (2018) Suppression of Wnt/β-catenin signaling by EGF receptor is required for hair follicle development. Mol Biol Cell 29:2784–2799

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tu Y, Wu T, Dai A, Pham Y, Chew P, de Haan JB et al (2011) Cell division autoantigen 1 enhances signaling and the profibrotic effects of transforming growth factor-beta in diabetic nephropathy. Kidney Int 79:199–209

    Article  CAS  PubMed  Google Scholar 

  • Turner CA, Sharma V, Hagenauer MH, Chaudhury S, O’Connor AM, Hebda-Bauer EK et al (2018) Connective tissue growth factor is a novel prodepressant. Biol Psychiatry 84:555–562

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Umanath K, Lewis JB (2018) Update on diabetic nephropathy: core curriculum 2018. Am J Kidney Dis 71:884–895

    Article  PubMed  Google Scholar 

  • van der Sande NG, Dorresteijn JA, Visseren FL, Dwyer JP, Blankestijn PJ, van der Graaf Y et al (2016) Individualized prediction of the effect of angiotensin receptor blockade on renal and cardiovascular outcomes in patients with diabetic nephropathy. Diab Obes Metab 18:1120–1127

    Article  CAS  Google Scholar 

  • Vasanthakumar R, Mohan V, Anand G, Deepa M, Babu S, Aravindhan V (2015) Serum IL-9, IL-17, and TGF-beta levels in subjects with diabetic kidney disease (CURES-134). Cytokine 72:109–112

    Article  CAS  PubMed  Google Scholar 

  • Verhave JC, Bouchard J, Goupil R, Pichette V, Brachemi S, Madore F et al (2013) Clinical value of inflammatory urinary biomarkers in overt diabetic nephropathy: a prospective study. Diabetes Res Clin Pract 101:333–340

    Article  CAS  PubMed  Google Scholar 

  • Voelker J, Berg PH, Sheetz M, Duffin K, Shen T, Moser B et al (2017) Anti-TGF-beta1 antibody therapy in patients with diabetic nephropathy. J Am Soc Nephrol 28:953–962

    Article  CAS  PubMed  Google Scholar 

  • Wahlang B, McClain C, Barve S, Gobejishvili L (2018) Role of cAMP and phosphodiesterase signaling in liver health and disease. Cell Signal 49:105–115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang S (2015) Role of upstream stimulatory factor 2 in diabetic nephropathy. Front Biol (Beijing) 10:221–229

    Article  CAS  Google Scholar 

  • Wang Y, Rangan GK, Tay YC, Wang Y, Harris DC (1999) Induction of monocyte chemoattractant protein-1 by albumin is mediated by nuclear factor kappaB in proximal tubule cells. J Am Soc Nephrol 10:1204–1213

    CAS  PubMed  Google Scholar 

  • Wang A, Ziyadeh FN, Lee EY, Pyagay PE, Sung SH, Sheardown SA et al (2007) Interference with TGF-beta signaling by Smad3-knockout in mice limits diabetic glomerulosclerosis without affecting albuminuria. Am J Physiol Renal Physiol 293:F1657–F1665

    Article  CAS  PubMed  Google Scholar 

  • Wang B, Herman-Edelstein M, Koh P, Burns W, Jandeleit-Dahm K, Watson A et al (2010) E-cadherin expression is regulated by miR-192/215 by a mechanism that is independent of the profibrotic effects of transforming growth factor-beta. Diabetes 59:1794–1802

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang B, Koh P, Winbanks C, Coughlan MT, McClelland A, Watson A et al (2011a) miR-200a prevents renal fibrogenesis through repression of TGF-beta2 expression. Diabetes 60:280–287

    Article  CAS  PubMed  Google Scholar 

  • Wang Q, Usinger W, Nichols B, Gray J, Xu L, Seeley TW et al (2011b) Cooperative interaction of CTGF and TGF-beta in animal models of fibrotic disease. Fibrogenesis Tissue Repair 4:4

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wang B, Komers R, Carew R, Winbanks CE, Xu B, Herman-Edelstein M et al (2012) Suppression of microRNA-29 expression by TGF-beta1 promotes collagen expression and renal fibrosis. J Am Soc Nephrol 23:252–265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang J, Gao Y, Ma M, Li M, Zou D, Yang J et al (2013) Effect of miR-21 on renal fibrosis by regulating MMP-9 and TIMP1 in kk-ay diabetic nephropathy mice. Cell Biochem Biophys 67:537–546

    Article  CAS  PubMed  Google Scholar 

  • Wang JY, Gao YB, Zhang N, Zou DW, Wang P, Zhu ZY et al (2014a) miR-21 overexpression enhances TGF-beta1-induced epithelial-to-mesenchymal transition by target smad7 and aggravates renal damage in diabetic nephropathy. Mol Cell Endocrinol 392:163–172

    Article  CAS  PubMed  Google Scholar 

  • Wang Z, Wei M, Wang M, Chen L, Liu H, Ren Y et al (2014b) Inhibition of macrophage migration inhibitory factor reduces diabetic nephropathy in type II diabetes mice. Inflammation 37:2020–2029

    Article  CAS  PubMed  Google Scholar 

  • Wei J, Zhang Y, Luo Y, Wang Z, Bi S, Song D et al (2014) Aldose reductase regulates miR-200a-3p/141-3p to coordinate Keap1-Nrf2, Tgfbeta1/2, and Zeb1/2 signaling in renal mesangial cells and the renal cortex of diabetic mice. Free Radic Biol Med 67:91–102

    Article  CAS  PubMed  Google Scholar 

  • White DA, Su Y, Kanellakis P, Kiriazis H, Morand EF, Bucala R et al (2014) Differential roles of cardiac and leukocyte derived macrophage migration inhibitory factor in inflammatory responses and cardiac remodelling post myocardial infarction. J Mol Cell Cardiol 69:32–42

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu CC, Sytwu HK, Lu KC, Lin YF (2011) Role of T cells in type 2 diabetic nephropathy. Exp Diabetes Res 2011:514738

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wu J, Zheng C, Fan Y, Zeng C, Chen Z, Qin W et al (2014) Downregulation of microRNA-30 facilitates podocyte injury and is prevented by glucocorticoids. J Am Soc Nephrol 25:92–104

    Article  CAS  PubMed  Google Scholar 

  • Wu H, Kong L, Tan Y, Epstein PN, Zeng J, Gu J et al (2016) C66 ameliorates diabetic nephropathy in mice by both upregulating NRF2 function via increase in miR-200a and inhibiting miR-21. Diabetologia 59:1558–1568

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xiao L, Wang M, Yang S, Liu F, Sun L (2013) A glimpse of the pathogenetic mechanisms of Wnt/beta-catenin signaling in diabetic nephropathy. Biomed Res Int 2013:987064

    PubMed  PubMed Central  Google Scholar 

  • Xie X, Xia W, Fei X, Xu Q, Yang X, Qiu D et al (2015) Relaxin inhibits high glucose-induced matrix accumulation in human mesangial cells by interfering with TGF-beta1 production and mesangial cells phenotypic transition. Biol Pharm Bull 38:1464–1469

    Article  CAS  PubMed  Google Scholar 

  • Xu W, Yang Z, Lu N (2015) A new role for the PI3K/Akt signaling pathway in the epithelial-mesenchymal transition. Cell Adh Migr 9:317–324

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yacoub R, Campbell KN (2015) Inhibition of RAS in diabetic nephropathy. Int J Nephrol Renovasc Dis 8:29–40

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yakush WJ (2017) Management strategies for patients with diabetic kidney disease and chronic kidney disease in diabetes. Nurs Clin North Am 52:575–587

    Article  Google Scholar 

  • Yang J, Dai C, Liu Y (2003) Hepatocyte growth factor suppresses renal interstitial myofibroblast activation and intercepts Smad signal transduction. Am J Pathol 163:621–632

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang Z, Guo Z, Dong J, Sheng S, Wang Y, Yu L et al (2018) miR-374a regulates inflammatory response in diabetic nephropathy by targeting MCP-1 expression. Front Pharmacol 9:900

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yano N, Suzuki D, Endoh M, Zhao TC, Padbury JF, Tseng YT (2007) A novel phosphoinositide 3-kinase-dependent pathway for angiotensin II/AT-1 receptor-mediated induction of collagen synthesis in MES-13 mesangial cells. J Biol Chem 282:18819–18830

    Article  CAS  PubMed  Google Scholar 

  • Yokoi H, Mukoyama M, Mori K, Kasahara M, Suganami T, Sawai K et al (2008) Overexpression of connective tissue growth factor in podocytes worsens diabetic nephropathy in mice. Kidney Int 73:446–455

    Article  CAS  PubMed  Google Scholar 

  • Zeisberg EM, Potenta SE, Sugimoto H, Zeisberg M, Kalluri R (2008) Fibroblasts in kidney fibrosis emerge via endothelial-to-mesenchymal transition. J Am Soc Nephrol 19:2282–2287

    Article  PubMed  PubMed Central  Google Scholar 

  • Zha D, Cheng H, Li W, Wu Y, Li X, Zhang L et al (2017) High glucose instigates tubulointerstitial injury by stimulating hetero-dimerization of adiponectin and angiotensin II receptors. Biochem Biophys Res Commun 493:840–846

    Article  CAS  PubMed  Google Scholar 

  • Zhang Z, Peng H, Chen J, Chen X, Han F, Xu X et al (2009) MicroRNA-21 protects from mesangial cell proliferation induced by diabetic nephropathy in db/db mice. FEBS Lett 583:2009–2014

    Article  CAS  PubMed  Google Scholar 

  • Zhang HT, Zhang D, Zha ZG, Hu CD (2014) Transcriptional activation of PRMT5 by NF-Y is required for cell growth and negatively regulated by the PKC/c-Fos signaling in prostate cancer cells. Biochim Biophys Acta 1839:1330–1340

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang C, Hou B, Yu S, Chen Q, Zhang N, Li H (2016a) HGF alleviates high glucose-induced injury in podocytes by GSK3beta inhibition and autophagy restoration. Biochim Biophys Acta 1863:2690–2699

    Article  CAS  PubMed  Google Scholar 

  • Zhang H, Li A, Zhang W, Huang Z, Wang J, Yi B (2016b) High glucose-induced cytoplasmic translocation of Dnmt3a contributes to CTGF hypo-methylation in mesangial cells. Biosci Rep 36

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhang Y, Sun X, Icli B, Feinberg MW (2017) Emerging roles for microRNAs in diabetic microvascular disease: novel targets for therapy. Endocr Rev 38:145–168

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang W, Hou X, Huang M, Zeng X, He X, Liao Y (2018) TDCPP protects cardiomyocytes from H2O2-induced injuries via activating PI3K/Akt/GSK3beta signaling pathway. Mol Cell Biochem

    Google Scholar 

  • Zhao B, Li H, Liu J, Han P, Zhang C, Bai H et al (2016) MicroRNA-23b targets Ras GTPase-activating protein SH3 domain-binding protein 2 to alleviate fibrosis and albuminuria in diabetic nephropathy. J Am Soc Nephrol 27:2597–2608

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhao D, Jia J, Shao H (2017a) miR-30e targets GLIPR-2 to modulate diabetic nephropathy: in vitro and in vivo experiments. J Mol Endocrinol 59:181–190

    Article  CAS  PubMed  Google Scholar 

  • Zhao Y, Yin Z, Li H, Fan J, Yang S, Chen C et al (2017b) MiR-30c protects diabetic nephropathy by suppressing epithelial-to-mesenchymal transition in db/db mice. Aging Cell 16:387–400

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zheng JM, Yao GH, Cheng Z, Wang R, Liu ZH (2012) Pathogenic role of mast cells in the development of diabetic nephropathy: a study of patients at different stages of the disease. Diabetologia 55:801–811

    Article  CAS  PubMed  Google Scholar 

  • Zhong X, Chung AC, Chen HY, Meng XM, Lan HY (2011) Smad3-mediated upregulation of miR-21 promotes renal fibrosis. J Am Soc Nephrol 22:1668–1681

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhong X, Chung AC, Chen HY, Dong Y, Meng XM, Li R et al (2013) miR-21 is a key therapeutic target for renal injury in a mouse model of type 2 diabetes. Diabetologia 56:663–674

    Article  CAS  PubMed  Google Scholar 

  • Zhou L, Liu Y (2016) Wnt/beta-catenin signaling and renin-angiotensin system in chronic kidney disease. Curr Opin Nephrol Hypertens 25:100–106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou T, He X, Cheng R, Zhang B, Zhang RR, Chen Y et al (2012) Implication of dysregulation of the canonical wingless-type MMTV integration site (WNT) pathway in diabetic nephropathy. Diabetologia 55:255–266

    Article  CAS  PubMed  Google Scholar 

  • Zhu L, Zhao S, Liu S, Liu Q, Li F, Hao J (2016) PTEN regulates renal extracellular matrix deposit via increased CTGF in diabetes mellitus. J Cell Biochem 117:1187–1198

    Article  CAS  PubMed  Google Scholar 

  • Ziyadeh FN, Hoffman BB, Han DC, Iglesias-De LCM, Hong SW, Isono M et al (2000) Long-term prevention of renal insufficiency, excess matrix gene expression, and glomerular mesangial matrix expansion by treatment with monoclonal antitransforming growth factor-beta antibody in db/db diabetic mice. Proc Natl Acad Sci U S A 97:8015–8020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zou XZ, Liu T, Gong ZC, Hu CP, Zhang Z (2017) MicroRNAs-mediated epithelial-mesenchymal transition in fibrotic diseases. Eur J Pharmacol 796:190–206

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China

    Ling-Feng Zeng, Ying Xiao & Lin Sun

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  1. Ling-Feng Zeng
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  2. Ying Xiao
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  1. Zhongda Hospital, Southeast University School of Medicine, Southeast University, Nanjing, Jiangsu, China

    Bi-Cheng Liu

  2. Department of Medicine and Therapeutics, Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, Hong Kong

    Hui-Yao Lan

  3. Zhongda Hospital, Southeast University School of Medicine, Southeast University, Nanjing, Jiangsu, China

    Lin-Li Lv

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Zeng, LF., Xiao, Y., Sun, L. (2019). A Glimpse of the Mechanisms Related to Renal Fibrosis in Diabetic Nephropathy. In: Liu, BC., Lan, HY., Lv, LL. (eds) Renal Fibrosis: Mechanisms and Therapies. Advances in Experimental Medicine and Biology, vol 1165. Springer, Singapore. https://doi.org/10.1007/978-981-13-8871-2_4

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