Park C, Lee M Y, Slivano O J, Park P J, Ha S, Berent R M, Fuchs R, Collins N C, Yu T J, Syn H, Park J K, Horiguchi K, Miano J M, Sanders K M, Ro S
Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV, USA.
Department of Physiology, Wonkwang Digestive Disease Research Institute and Institute of Wonkwang Medical Science, School of Medicine, Wonkwang University, Iksan, Jeollabuk-do, Korea.
Cell Death Dis. 2015 Dec 3;6(12):e2011. doi: 10.1038/cddis.2015.353.
Serum response factor (SRF) is a transcription factor known to mediate phenotypic plasticity in smooth muscle cells (SMCs). Despite the critical role of this protein in mediating intestinal injury response, little is known about the mechanism through which SRF alters SMC behavior. Here, we provide compelling evidence for the involvement of SRF-dependent microRNAs (miRNAs) in the regulation of SMC apoptosis. We generated SMC-restricted Srf inducible knockout (KO) mice and observed both severe degeneration of SMCs and a significant decrease in the expression of apoptosis-associated miRNAs. The absence of these miRNAs was associated with overexpression of apoptotic proteins, and we observed a high level of SMC death and myopathy in the intestinal muscle layers. These data provide a compelling new model that implicates SMC degeneration via anti-apoptotic miRNA deficiency caused by lack of SRF in gastrointestinal motility disorders.
血清反应因子（SRF）是一种已知可介导平滑肌细胞（SMC）表型可塑性的转录因子。尽管该蛋白在介导肠道损伤反应中起关键作用，但关于SRF改变SMC行为的机制却知之甚少。在此，我们提供了令人信服的证据，证明SRF依赖性微小RNA（miRNA）参与了SMC凋亡的调控。我们构建了平滑肌细胞特异性的Srf诱导型敲除（KO）小鼠，并观察到SMC严重退化以及凋亡相关miRNA的表达显著降低。这些miRNA的缺失与凋亡蛋白的过表达相关，并且我们在肠道肌层中观察到高水平的SMC死亡和肌病。这些数据提供了一个令人信服的新模型，表明在胃肠动力障碍中，由于缺乏SRF导致抗凋亡miRNA缺乏，从而引发SMC退化。
