Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada, United States of America.
PLoS One. 2011 Apr 14;6(4):e18628. doi: 10.1371/journal.pone.0018628.
Smooth muscle cells (SMCs) express a unique set of microRNAs (miRNAs) which regulate and maintain the differentiation state of SMCs. The goal of this study was to investigate the role of miRNAs during the development of gastrointestinal (GI) SMCs in a transgenic animal model. We generated SMC-specific Dicer null animals that express the reporter, green fluorescence protein, in a SMC-specific manner. SMC-specific knockout of Dicer prevented SMC miRNA biogenesis, causing dramatic changes in phenotype, function, and global gene expression in SMCs: the mutant mice developed severe dilation of the intestinal tract associated with the thinning and destruction of the smooth muscle (SM) layers; contractile motility in the mutant intestine was dramatically decreased; and SM contractile genes and transcriptional regulators were extensively down-regulated in the mutant SMCs. Profiling and bioinformatic analyses showed that SMC phenotype is regulated by a complex network of positive and negative feedback by SMC miRNAs, serum response factor (SRF), and other transcriptional factors. Taken together, our data suggest that SMC miRNAs are required for the development and survival of SMCs in the GI tract.
平滑肌细胞（SMCs）表达一组独特的 microRNAs（miRNAs），这些 miRNAs 调节和维持 SMC 的分化状态。本研究的目的是在转基因动物模型中研究 miRNAs 在胃肠道（GI）SMC 发育过程中的作用。我们生成了 SMC 特异性 Dicer 缺失动物，这些动物以 SMC 特异性的方式表达报告基因，绿色荧光蛋白。SMCs 中 Dicer 的特异性敲除阻止了 SMC miRNA 的生物发生，导致 SMC 表型、功能和整体基因表达发生剧烈变化：突变小鼠的肠道出现严重扩张，与平滑肌（SM）层的变薄和破坏有关；突变肠中的收缩运动明显减少；SM 收缩基因和转录调节剂在突变 SMC 中广泛下调。分析和生物信息学分析表明，SMC 表型受 SMC miRNAs、血清反应因子（SRF）和其他转录因子的正反馈和负反馈的复杂网络调节。总之，我们的数据表明，SMC miRNAs 是 GI 道中 SMC 发育和存活所必需的。
