MicroRNA Regulation of Smooth Muscle Phenotype.
MicroRNA Regulation of Smooth Muscle Phenotype.
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发表时间：
2012
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通讯作者：
S. Joshi;B. S. Comer;J. McLendon;W. Gerthoffer
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作者：
S. Joshi;B. S. Comer;J. McLendon;W. Gerthoffer
平滑肌microRNA（microRNA，miRNA）表达和功能的研究进展表明，小分子非编码RNA对细胞增殖、肥大和分化具有重要作用。在包括平滑肌在内的多种细胞类型中，miRNA研究的一个新兴主题是miRNA调节蛋白质表达网络以微调表型。已经描述了一些在平滑肌中广泛表达的miRNA，其调节许多细胞类型中的重要过程，例如miR-21对增殖和细胞存活的控制。作为平滑肌限制性基因表达的主要调节因子的其他miRNA也具有控制多能细胞分化的靶点。miR-143~145簇靶向于心肌蛋白和Kruppel样因子4（KLF 4），是平滑肌中描述最多的miRNA家族，对促进血清反应因子（SRF）依赖性收缩和细胞骨架蛋白表达的基因表达网络以及成熟收缩表型具有深远影响。Kruppel家族成员KLF 4和KLF 5对细胞分化具有多种作用，并且是平滑肌中多种miRNA（miR-145、miR-146 a、miR-25）的靶标。被定义的反馈和前馈回路似乎对心血管和呼吸系统疾病中的血管和气道重塑有显著贡献。应用于血管和呼吸道疾病动物模型的RNA干扰方法证明，miRNA和RNA诱导的沉默是改变病理性平滑肌增生和肥大的新型抗重塑疗法的有效靶点。
Advances in studies of microRNA (miRNA) expression and function in smooth muscles illustrate important effects of small noncoding RNAs on cell proliferation, hypertrophy and differentiation. An emerging theme in miRNA research in a variety of cell types including smooth muscles is that miRNAs regulate protein expression networks to fine tune phenotype. Some widely expressed miRNAs have been described in smooth muscles that regulate important processes in many cell types, such as miR-21 control of proliferation and cell survival. Other miRNAs that are prominent regulators of smooth muscle-restricted gene expression also have targets that control pluripotent cell differentiation. The miR-143~145 cluster which targets myocardin and Kruppel-like factor 4 (KLF4) is arguably the best-described miRNA family in smooth muscles with profound effects on gene expression networks that promote serum response factor (SRF)-dependent contractile and cytoskeletal protein expression and the mature contractile phenotype. Kruppel-family members KLF4 and KLF5 have multiple effects on cell differentiation and are targets for multiple miRNAs in smooth muscles (miR-145, miR-146a, miR-25). The feedback and feedforward loops being defined appear to contribute significantly to vascular and airway remodeling in cardiovascular and respiratory diseases. RNA interference approaches applied to animal models of vascular and respiratory diseases prove that miRNAs and RNA-induced silencing are valid targets for novel anti-remodeling therapies that alter pathological smooth muscle hyperplasia and hypertrophy.