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- W2955792254 abstract "Renal fibrosis is a common pathway for the progression of various chronic kidney diseases (CKD) to end-stage kidney disease (ESKD). Ferroptosis is a novel non-programmed cell death driven by iron-based lipid peroxidation, which is closely related to diseases such as tumor and ischemia-reperfusion injury, but its role in renal fibrosis is unknown. In this study, we explored the expression and the potential role of ferroptosis in renal fibrosis in CKD patients,TGF-b-treated tubular epithelial cells (TECs) and the obstructive nephropathy mouse model. The kidney tissues from renal biopsy-proved renal fibrosis patients including IgA nephropathy (IgAN) and diabetic nephropathy (DN) was collected to examine the expression of ferroptosis negatively related indexes such as glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) by immunohistochemistry staining (IHC), while the morphological changes of ferroptosis was observed by electron microscopy, and the minimal change disease (MCD) as control. In addition, the morphology of ferroptosis and expression of GPX4 and SLC7A11were also detected both in TGF-β-stimulated human renal tubular epithelial cells (HK2) and unilateral ureteral obstruction (UUO) mouse model by electron microscopy and IHC, Western blot, quantitative real-time polymerase chain reaction (qRT-PCR), respectively. Moreover, the ferroptosis was induced or inhibited by ferroptosis agonist Erastin and inhibitor Ferrostatin in HK2 and then renal fibrosis markers of fibronectin (FN), collagen I (Col I) and α-smooth muscle actin (α- SMA) were further detected by Western blot and qRT-PCR. Compared to the MCD, the kidney tissues of IgAN and DN showed different degrees of glomerular sclerosis, renal interstitial fibrosis, and deposition of a large number of extracellular matrix and collagen fibers by HE, PAS and Masson staining. The ferroptosis morphological changes such as the shrucked volume of mitochondria, a reduced number of cristae and an increased density of bilayer membrane were observed in IgAN and DN renal tissue by electron microscopy. The expression of GPX4 and SLC7A11 were significantly decreased in IgAN and DN patients, unilateral ureteral obstruction (UUO) mouse model and TGF-β-stimulated HK2 cells. After ferroptosis induced by Erastin, the renal fibrosis markers of FN, Col I and α-SMA were significantly enhanced after TGF-β treatment for 24 hours, while the renal fibrosis was decreased by ferroptosis inhibitor Ferrostatin. Ferroptosis is expressed in renal fibrosis in CKD patients and in TGF-b-treated tubular epithelial cells (TECs) and the obstructive nephropathy mouse model. The intervention of ferroptosis by agonist and inhibitor has effect on the renal fibrosis in HK2 cells. These data indicates that the potential role of ferroptosisin renal fibrosis." @default.
- W2955792254 created "2019-07-12" @default.
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- W2955792254 date "2019-07-01" @default.
- W2955792254 modified "2023-09-26" @default.
- W2955792254 title "SUN-154 The Expression and Significance of Ferroptosis in Renal Fibrosis" @default.
- W2955792254 doi "https://doi.org/10.1016/j.ekir.2019.05.555" @default.
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