ALKBH5 ameliorates renal interstitial fibrosis in mouse models with unilateral ureteral obstruction by regulating the expression of Fdx1

doi:10.16352/j.issn.1001-6325.2026.07.0950

Abstract

Abstract: Objective To explore the effect of alkylated repair(RNA demethylase ALKB) homologue 5 (ALKBH5) to regulate the expression of cuproptosis-related gene ferredoxin 1 (Fdx1) on renal interstitial fibrosis (RIF) in unilateral ureteral obstruction (UUO) mice. Methods The UUO model mice were randomly divided into a model group (UUO group), a negative control group (LV5-vector group), an ALKBH5 over-expression group (LV5-ALKBH5 group), an LV5-vector+ FDX1 activator (Elesclomol) group and an LV5-ALKBH5+Elesclomol group, with 12 mice in each .Another 12 healthy mice were taken as control group (control group). ELISA kit was used to detect serum inflammatory factor; HE and Masson staining microscopy was used to observe renal histopathological changes and fibrosis; RT-qPCR detection of epithelial-mesenchymal transition (EMT)-related genes and Alkbh5 and Fdx1 mRNA expression in renal tissue epithelial cells; The expression of ALKBH5 and FDX1 protein were detected by immunoblotting. Results Compared with the control group, mice in the UUO group showed increased renal tissue lesions, increased percentage of fibrosis (P＜0.05), increased serum renal function indexes; Higher level of inflammation factor and renal tissue α-SMA, snail and FDX1 expression (P＜0.05), and decreased E-cadherin and ALKBH5 expression (P＜0.05).Compared with the LV5-vector group, mice in the LV5-ALKBH5 group showed significantly improved results on above indexes (P＜0.05). Over-expression of ALKBH5 was reversed which promoted FDX1 activation on renal tissue inflammation, EMT and renal interstitial fibrosis in UUO mice. Conclusions ALKBH5 may attenuate the inflammatory response, inhibit EMT, ameliorate kidney injury, and alleviate RIF in UUO mice by down-regulating the expression of the cuproptosis-related gene Fdx1.

Key words: unilateral ureteral obstruction, renal interstitial fibrosis, alkylated repair homologue 5 (ALKBH5), ferredoxin 1 (FDX1), cuproptosis

CLC Number:

R691.2

HOU Donghua, WU Qi, LIANG Hui, BAO Nana, LYU Huiyan, DAI Deyu, ZHANG Lei. ALKBH5 ameliorates renal interstitial fibrosis in mouse models with unilateral ureteral obstruction by regulating the expression of Fdx1[J]. Basic & Clinical Medicine, 2026, 46(7): 950-956.

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