한빛사 논문
Abstract
Chanjae Park1, Wei Yan1, Sean M. Ward1, Sung Jin Hwang1, Qiuxia Wu1, William J. Hatton1, Jong Kun Park2, Kenton M. Sanders1, Seungil Ro1*
1 Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada, United States of America, 2 Division of Biological Science, Wonkwang University, Iksan, Chonbuk, South Korea
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.
Citation: Park C, Yan W, Ward SM, Hwang SJ, Wu Q, et al. (2011) MicroRNAs Dynamically Remodel Gastrointestinal Smooth Muscle Cells. PLoS ONE 6(4): e18628. doi:10.1371/journal.pone.0018628
Editor: Sumitra Deb, Virginia Commonwealth University, United States of America
Received: November 11, 2010; Accepted: March 8, 2011; Published: April 14, 2011
Copyright: ⓒ 2011 Park et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was supported by the NIH grant P20 RR018751 to K.M. Sanders and HD048855, HD60858, and HD050281 to W. Yan, and an equipment grant from the NCRR for a Zeiss LSM510 confocal microscope (1 S10 RR16871) was used for the morphological studies. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
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