Interventional effect  of epalrestat on renal interstitial fibrosis in  unilateral ureteral obstruction rats and its mechanism

doi:10.12047/j.cjap.5735.2019.019

Abstract

Abstract: Objective:To observe the protective effects of epalrestat (EPS) on interstitial fibrosis in unilateral ureteral obstruction (UUO) rats and its mechanism.Methods: Rats were randomly divided into four groups: sham group, UUO group, UUO + epalrestat (50 or 100 mg/kg), 8 rats in each group.Rats in UUO and UUO + epalrestat group were obstructed left ureter.In the sham group, rats had their left ureters exposed and manipulated without ligation.Animals for epalrestat treatment received daily drug via gavage for 3 weeks, the rats of sham and UUO groups received equal amount of sodium carboxymethyl cellulose with the same regimen.Renal tissues pathological changes and collagen deposition were observed by HE and Masson's staining.The aldose reductase(AR) expression in renal tissues was measured by immunohistochemisty.The expression levels of collagen I, collagen III, alpha-smooth muscle actin (α-SMA), fibroblast-specific protein1 (FSP-1), fibronectin (FN), epithelial cadherin (E-cadherin), transforming growth factor-β1 (TGF-β1) and AR from kidney tissues were measured by real-time RT-PCR or Western blot.Results: Compared with the sham group, the renal tissues of the UUO group showed significant fibrosis, including renal tubular epithelial cell atrophy and vacuolated degeneration, collagen deposition, fibroblasts and myofibroblasts proliferation and inflammatory cell infiltration, and concomitantly with the expressions of collagen I, collagen III, TGF-β1, AR, α-SMA, FSP-1 and FN were remarkably up-regulated, but E-cadherin was significantly reduced in UUO group.Compared with the UUO group, after 3 weeks epalrestat administration, the level of renal interstitial fibrosis was obviously ameliorated and the expressions of collagen I, collagen III, TGF-β1, AR, α-SMA, FSP-1 and FN were remarkably down-regulated, but E-cadherin was significantly increased in rats of epalrestat groups.Conclusion: These results suggest that epalrestat attenuates renal interstitial fibrosis possibly through inhibition of EMT via inhibiting TGF-β1 and AR expression.

Key words: epalrestat, ureteral obstruction, renal interstitial fibrosis, epithelial-mesenchymal transition, rat

GAO Yun-xing, TANG Juan, ZHANG Qian, JIANG Li-li , LI Xian-wei. Interventional effect of epalrestat on renal interstitial fibrosis in unilateral ureteral obstruction rats and its mechanism[J]. CJAP, 2019, 35(1): 79-84.

References

[1]Becker GJ, Hewitson TD. The role of tubulointerstitial injury in chronic renal failure[J]. Curr Opin Nephrol Hypertens, 2000, 9(2): 133-138.
[2]Farris AB, Colvin RB. Renal interstitial fibrosis: mechanisms and evaluation[J]. Curr Opin Nephrol Hypertens, 2012, 21(3): 289-300.
[3]Song Y, Peng CL, Lv S, et al. Adipose-derived stem cells ameliorate renal interstitial fibrosis through inhibition of EMT and inflammatory response via TGF-β1 signaling pathway[J]. Int Immunopharmacol, 2017, 44: 115-122.
[4]Reddy AB, Tammali R, Mishra R, et al. Aldose reductase deficiency protects sugar-induced lens opacification in rats[J]. Chem Biol Interact, 2011, 191(1-3): 346-350.
[5]Kagami S. Involvement of glomerular renin-angiotensin system (RAS) activation in the development and progression of glomerular injury[J]. Clin Exp Nephrol, 2012, 16(2): 214-220.
[6]Zou L, Wang W, Xu Z, et al. Aldose reductase regulates platelet-derived growth factor-induced proliferation through mediating cell cycle progression in rat mesangial cells[J]. Int J Mol Med, 2012, 30(2): 409-416.
[7]Li X, Shen Y, Lu Y, et al. Amelioration of Bleomycin-induced pulmonary fibrosis of rats by an aldose reductase inhibitor, epalrestat[J]. Korean J Physiol Pharmacol, 2015, 19(5): 401-411.
[8]Hotta N, Kawamori R, Atsumi Y, et al. Stratified analyses for selecting appropriate target patients with diabetic peripheral neuropathy for long-term treatment with an aldose reductase inhibitor, epalrestat[J]. Diabet Med, 2008, 25(7): 818-825.
[9]He J, Gao HX, Yang N, et al. The aldose reductase inhibitor epalrestat exerts nephritic protection on diabetic nephropathy in db/db mice through metabolic modulation[J]. Acta Pharmacol Sin, 2019, 40（1）: 86-97.
[10]李先伟，汪向明，李曙，等. 吴茱萸次碱对肺动脉高压大鼠右心室重构的影响[J]. 中国应用生理学杂志, 2014, 30(5): 405-410.
[11]Qi W, Chen X, Poronnik P, et al. The renal cortical fibroblast in renal tubulointerstitial fibrosis[J]. Int J Biochem Cell Biol, 2006, 38(1): 1-5.
[12]Teng JF, Wang K, Li Y, et al. Conditional knockout of src homology 2 domain-containing protein tyrosine phosphatase-2 in myeloid cells attenuates renal fibrosis after unilateral ureter obstruction[J]. Chin Med J (Engl), 2015, 128(9): 1196-1201.
[13]Grewal AS, Bhardwaj S, Pandita D, et al. Updates on aldose reductase inhibitors for management of diabetic complications and non-diabetic diseases[J]. Mini Rev Med Chem, 2016, 16(2): 120-162.
[14]Allison SJ.Fibrosis: Targeting EMT to reverse renal fibrosis[J]. Nat Rev Nephrol, 2015, 11(10): 565.
[15]Meng XM, Tang PM, Li J, et al. TGF-β/Smad signaling in renal fibrosis[J]. Front Physiol, 2015, 6: 82.
[16]Huang P, Zhang Y, Jiang T, et al. Aldose reductase is a potent regulator of TGF-β1 induced expression of fibronectin in human mesangial cells[J]. Mol Biol Rep, 2010, 37(7): 3097-3103.
[17]Zhang Y, Huang P, Jiang T, et al. Role of aldose reductase in TGF-beta1-induced fibronectin synthesis in human mesangial cells[J]. Mol Biol Rep, 2010, 37(6): 2735-2742.

Interventional effect of epalrestat on renal interstitial fibrosis in unilateral ureteral obstruction rats and its mechanism

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