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MircroRNA-92b, a Novel Negative Regulator of the Transforming Growth Factor-β Signaling Pathway Targeting the Type I Receptor

ABSTRACT: Progressive renal disease is the consequence of destructive fibrosis. Renal fibrosis is a common outcome of many chronic kidney diseases, including diabetic kidney disease (DKD). Transforming growth factor-β1 (TGFβ1) has been identified as a major pathogenic factor underlying the development of DKD. It had been reported that the expression of miR-92b-3p had been reported to be reduced in the kidneys from diabetic mice and patients with DKD. However, the role of miR-92b-3p in the progress of renal fibrosis was remaining largely unknown. This study investigated the role of miR-92b-3p in the progression of renal fibrosis in unilateral ureteral occlusion (UUO) and unilateral ischemia-reperfusion injury (uIRI) mouse models, as well as explored its underlying mechanisms in human proximal tubular epithelial (HK2) cells. We found that renal fibrosis increased in UUO mice after miR-92b knockout, while reduced in miR-92b overexpressing mice. MiR-92b knockout aggravated renal fibrosis in unilateral ischemia-reperfusion injury. RNA-sequencing analysis, the luciferase reporter assay, qPCR analysis, and western blotting confirmed that miR-92b-3p directly targeted TGF-β receptor 1 (TGFBR1), thereby ameliorating renal fibrosis by suppressing the TGF-β/SMAD3 signaling pathway. Furthermore, we found that TGF-β suppressed miR-92b transcription through Snail family transcriptional repressors 1 (SNAI1) and SNAI2. Our results suggest that miR-92b-3p may serve as a novel therapeutic for mitigating fibrosis in chronic kidney disease.

ORGANISM(S): Mus musculus

PROVIDER: GSE242295 | GEO | 2023/10/01

REPOSITORIES: GEO

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