Iguratimod alleviates tubulo-interstitial injury in mice with lupus

Autor: Leixi Xue, Jiajun Xu, Wentian Lu, Jinxiang Fu, Zhichun Liu
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Renal Failure, Vol 44, Iss 1, Pp 636-647 (2022)
Druh dokumentu: article
ISSN: 0886022X
1525-6049
0886-022X
DOI: 10.1080/0886022X.2022.2058962
Popis: Introduction Tubulo-interstitial injury is a poor prognostic factor for lupus nephritis (LN). Here, we tested whether iguratimod could inhibit tubulo-interstitial injury in LN.Methods MRL/lpr mice, an animal model of lupus, were treated with iguratimod or vehicle solution. Pathological changes of kidney were evaluated blindly by the same pathologist. Renal type I collagen (COL-I), IgG, E-cadherin, fibroblast-specific protein 1 (FSP-1) were detected by immunofluorescence, immunohistochemical staining or quantitative real-time PCR. After treated with transforming growth factor β1 (TGF-β1) and iguratimod, E-cadherin, fibronectin, Smad2/3, p38 MAPK, p-Smad2/3, and p-p38 MAPK, β-catenin and TGF-β type II receptor (TGFβRII) in HK2 cells were measured by western blotting, quantitative real-time PCR or immunofluorescence.Results Iguratimod reduced immune deposition along the tubular basement membrane, inhibited the tubulo-interstitial infiltration of inflammatory cells, and alleviated tubular injury in MRL/lpr mice. Moreover, Iguratimod eased the tubulo-interstitial deposition of collagen fibers, which was confirmed by decreased expression of COL-I. Furthermore, iguratimod suppressed the expression of FSP-1 and increased that of E-cadherin in renal tubular epithelial cells. In HK2 cells cultured with TGF-β1, iguratimod treatment not only reversed cellular morphological changes, but also prevented E-cadherin downregulation and fibronectin upregulation. In addition, iguratimod inhibited phosphorylation of TGFβRII, Smad2/3 and p38 MAPK in HK2 cells treated with TGF-β1, and also blocked nuclear translocation of β-catenin.Conclusion Iguratimod eased tubulo-interstitial lesions in LN, especially tubulo-interstitial fibrosis, and might have potential as a drug for inhibiting the progression of tubulo-interstitial fibrosis in LN.
Databáze: Directory of Open Access Journals
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