Asiaticoside inhibits renal fibrosis development by regulating the miR-142-5p/ACTN4 axis.

Abstract

Renal fibrosis results in the progressive renal dysfunction and leads to chronic kidney disease (CKD) and ultimately end-stage renal disease. Asiaticoside was reported to regulate synaptopodin, desmin, nephrin, and podocin levels in adriamycin-induced nephropathy of rats. In this study, we found out that asiaticoside inhibited renal fibrosis in vitro and in vivo. Additionally, miR-142-5p was upregulated in in vitro and in vivo models of CKD. MiR-142-5p promoted the levels of collagen-I, collagen-IV, and fibronectin proteins. Additionally, miR-142-5p overexpression partly rescued the protective effect of asiaticoside on renal fibrosis. Mechanistically, miR-142-5p inhibited ACTN4 levels by binding with its 3´untranslated region, and further reduced its translation. Treatment of asiaticoside decreased miR-142-5p levels and increased ACTN4 levels. Rescue assays revealed that ACTN4 overexpression partially rescued the effect of miR-142-5p on renal fibrosis. Asiaticoside mitigated renal fibrosis by regulating the miR-142-5p/ACTN4 axis. In conclusion, asiaticoside inhibits renal fibrosis by regulating the miR-142-5p/ACTN4 axis. This novel discovery suggested that asiaticoside may serve as a potential medicine for renal fibrosis improvement.

• Authors: Min Zhang, Shuhuan Liu, Liming Fang, Gang Wang, Liping Yin
• Journal: Biotechnology and applied biochemistry (Biotechnol Appl Biochem) Vol. 69 Issue 1 Pg. 313-322 (Feb 2022) ISSN: 1470-8744 [Electronic] United States
• PMID: 33444480 (Publication Type: Journal Article, Retracted Publication)
• Copyright: © 2021 International Union of Biochemistry and Molecular Biology, Inc.

Chemical References

• Actn4 protein, rat
• MIRN142 microRNA, rat
• MicroRNAs
• Triterpenes
• Actinin
• asiaticoside

Topics

• Actinin
• Animals
• Fibrosis
• Kidney Diseases (chemically induced, drug therapy, genetics)
• MicroRNAs (genetics)
• Rats
• Triterpenes