Abolhasani Sakhavat, Ahmadi Yasin, Rostami Yavar, Fattahi Davood
Department of Basic Sciences and Health, Sarab Faculty of Medical Sciences, Sarab, East Azerbaijan, Iran.
Department of Medical Laboratory Science, Komar University of Sciences and Technology, Sulaymaniyah, Kurdistan Region, Iraq.
Cell Div. 2025 Mar 7;20(1):6. doi: 10.1186/s13008-025-00146-0.
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.
微小RNA（miRNA）是一类小的非编码RNA分子，在调节基因表达中起着至关重要的作用，尤其是在间充质干细胞（MSC）向血管平滑肌细胞（VSMC）的分化过程中。鉴于MSC在特定分子信号作用下能够分化为平滑肌细胞（SMC），它们在血管修复和再生医学方面具有巨大的潜力。最近的研究表明，miRNA通过复杂的调控网络，靶向关键信号通路并调节分化标志物的表达，从而影响MSC的分化，凸显了这些分子在细胞发育中的复杂作用。本综述全面研究了各种miRNA在MSC分化中的功能，重点关注miR-143和miR-145，它们由转化生长因子β1（TGF-β1）上调，而TGF-β1是SMC发育中的关键生长因子。这些miRNA通过促进SMC标志物（包括α-平滑肌肌动蛋白（α-SMA）和钙调蛋白）的表达以及抑制使MSC保持未分化状态的因子来增强分化。本综述还讨论了miR-503的作用，它通过TGF-β途径抑制SMAD7来支持SMC分化，以及miR-222-5p的作用，它通过下调ROCK2和α-SMA来对抗分化。通过强调这些调控机制，本综述旨在阐明miRNA在VSMC分化中的双向和多方面作用。这项研究为miRNA介导的MSC分化在血管修复和再生中的治疗潜力提供了见解，最终有助于改善心血管疾病的治疗效果。
