The role of MicroRNAs in mesenchymal stem cell differentiation into vascular smooth muscle cells

Abstract

Abstract MicroRNAs (miRNAs) are small, noncoding RNA molecules that play a vital role in regulating gene expression, especially in the differentiation of mesenchymal stem cells (MSCs) into vascular smooth muscle cells (VSMCs). MSCs hold considerable promise for vascular repair and regenerative medicine, given their ability to differentiate into smooth muscle cells (SMCs) under specific molecular cues. Recent studies have shown that miRNAs, through complex regulatory networks, influence MSC differentiation by targeting essential signaling pathways and modulating the expression of differentiation markers, underscoring the intricate roles of these molecules in cellular development. This review comprehensively examines the functions of various miRNAs in MSC differentiation, focusing on miR-143 and miR-145, which are upregulated by transforming growth factor beta 1 (TGF-β1), a key growth factor in SMC development. These miRNAs enhance differentiation by promoting the expression of SMC markers, including α-smooth muscle actin (α-SMA) and calponin, and by inhibiting factors that preserve MSCs in an undifferentiated state. This review further discusses the roles of miR-503, which supports SMC differentiation through SMAD7 inhibition via the TGF-β pathway, and miR-222-5p, which counteracts differentiation by downregulating ROCK2 and α-SMA. By highlighting these regulatory mechanisms, this review aims to clarify the bidirectional and multifaceted role of miRNAs in VSMC differentiation. This study offers insights into the therapeutic potential of miRNA-mediated MSC differentiation for vascular repair and regeneration, ultimately contributing to improved cardiovascular outcomes.

Keywords

• MicroRNAs (miRNAs)
• Mesenchymal stem cells (MSCs)
• Vascular smooth muscle cells (VSMCs)
• Differentiation