Mir-195-5p targets Smad7 regulation of the Wnt/β-catenin pathway to promote osteogenic differentiation of vascular smooth muscle cells

BMC Cardiovasc Disord. 2024 Apr 23;24(1):221. doi: 10.1186/s12872-024-03891-2.

Abstract

In this study, we sought to investigate the mechanisms of action of miR-195-5p in the osteogenic differentiation of vascular smooth muscle cells (VSMCs), and thereby provide novel insights and a reference for the targeted therapy of arterial media calcification. VSMC differentiation was induced using sodium β-glycerophosphate, and we investigated the effects of transfecting cells with miR-195-5p mimics, vectors overexpressing Smad7, and the Wnt/β-catenin pathway inhibitor (KYA1797K) on VSMC differentiation by determining cell viability and apoptosis, and the mRNA and protein expression of factors associated with osteogenic differentiation and the Wnt/β-catenin pathway. The results revealed that miR-195-5p mimics enhanced the osteogenic differentiation of VSMCs induced by β-glycerophosphate, whereas the overexpression of Smad7 reversed this phenomenon. In addition, KYA1797K was found to promote the effects of Smad7 overexpression. In conclusion, by targeting, Smad7, miR-195-5p promotes the Wnt/β-catenin pathway. and thus the osteogenic differentiation of VSMCs. These findings will provide a reference for elucidating the mechanisms whereby miR-195-5p regulates osteogenic differentiation.

Keywords: Osteogenic differentiation; Smad7; VSMCs; Wnt/β-catenin pathway; miR-195-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Differentiation*
  • Cells, Cultured
  • Gene Expression Regulation
  • Glycerophosphates / pharmacology
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Muscle, Smooth, Vascular* / cytology
  • Muscle, Smooth, Vascular* / metabolism
  • Myocytes, Smooth Muscle* / drug effects
  • Myocytes, Smooth Muscle* / metabolism
  • Osteogenesis* / genetics
  • Rats
  • Smad7 Protein* / genetics
  • Smad7 Protein* / metabolism
  • Wnt Signaling Pathway*
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • beta Catenin
  • beta-glycerophosphoric acid
  • Glycerophosphates
  • MicroRNAs
  • Smad7 Protein
  • MIRN195 microRNA, rat
  • Smad7 protein, rat