MicroRNA-668 Alleviates Renal Fibrosis Through PPARα/PGC-1α Pathway

Overview

Journal Eur J Med Res

Publisher Biomed Central

Specialty General Medicine

Date 2024 Dec 28

PMID 39732711

Authors

Xinran Wang

Zhoupeng Gu

Yan Huang

Jingyan Wang

Shiqi Tang

Xinyu Yang

Jianwen Wang

Affiliations

Soon will be listed here.

Abstract

Background: The involvement of microRNA-668 (miR-668) in the onset and progression of renal fibrosis remains unclear. To this end, we aimed to explore the relevant mechanism of miR-668 in renal fibrosis.

Methods: C57BL/6 J male mice were randomly divided into sham-operated, unilateral ureteral obstruction (UUO), and UUO-fenofibrate groups. Based on transfection and drug intervention, HK-2 cells were divided into blank control, TGF-β1, TGF-β1 + fenofibrate (PPARα agonist), mimics-NC, miR-668, mimics-NC + TGF-β1, miR-668 + TGF-β1, miR-668 + TGF-β1 + fenofibrate, miR-668 + TGF-β1 + GW6471 (PPARα inhibitor), mimics-NC + TGF-β1 + fenofibrate, and mimics-NC + TGF-β1 + GW6471 groups. The pathological changes in the renal tissues were observed by hematoxylin-eosin (HE) and Masson staining. The expression of PPARα, PGC-1α, miR-668, E-cadherin, Collagen III (Col III), and α-SMA in the renal tissues or HK-2 cells was detected by western blot, immunohistochemical analyses or real-time quantitative polymerase chain reaction. The regulatory effect of miR-668 on PPARα was verified by dual-luciferase reporter assay.

Results: The expression of PPARα and PGC-1α decreased in UUO mice and TGF-β1-induced HK-2 cells, which was improved by fenofibrate. Compared to the non-transfected group, in TGF-β1-stimulated HK-2 cells, the expression of E-cadherin, PPARα and PGC-1α increased and the expression of Col III and α-SMA decreased in the miR-668-transfected group. The dual-luciferase reporter assay indicated the regulatory effect of hsa-mir-668-3p on PPARα.

Conclusion: MiR-668 can target PPARα and positively regulate the PPARα/PGC-1α pathway to alleviate renal fibrosis.

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