MicroRNAs dynamically remodel gastrointestinal smooth muscle cells.

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-specif...

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Main Authors: Chanjae Park, Wei Yan, Sean M Ward, Sung Jin Hwang, Qiuxia Wu, William J Hatton, Jong Kun Park, Kenton M Sanders, Seungil Ro
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-04-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3077387?pdf=render
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author Chanjae Park
Wei Yan
Sean M Ward
Sung Jin Hwang
Qiuxia Wu
William J Hatton
Jong Kun Park
Kenton M Sanders
Seungil Ro
author_facet Chanjae Park
Wei Yan
Sean M Ward
Sung Jin Hwang
Qiuxia Wu
William J Hatton
Jong Kun Park
Kenton M Sanders
Seungil Ro
author_sort Chanjae Park
collection DOAJ
description 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.
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spelling doaj.art-0edfdd3b553544cca185fd0d78dfb6902022-12-22T00:11:26ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-04-0164e1862810.1371/journal.pone.0018628MicroRNAs dynamically remodel gastrointestinal smooth muscle cells.Chanjae ParkWei YanSean M WardSung Jin HwangQiuxia WuWilliam J HattonJong Kun ParkKenton M SandersSeungil RoSmooth 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.http://europepmc.org/articles/PMC3077387?pdf=render
spellingShingle Chanjae Park
Wei Yan
Sean M Ward
Sung Jin Hwang
Qiuxia Wu
William J Hatton
Jong Kun Park
Kenton M Sanders
Seungil Ro
MicroRNAs dynamically remodel gastrointestinal smooth muscle cells.
PLoS ONE
title MicroRNAs dynamically remodel gastrointestinal smooth muscle cells.
title_full MicroRNAs dynamically remodel gastrointestinal smooth muscle cells.
title_fullStr MicroRNAs dynamically remodel gastrointestinal smooth muscle cells.
title_full_unstemmed MicroRNAs dynamically remodel gastrointestinal smooth muscle cells.
title_short MicroRNAs dynamically remodel gastrointestinal smooth muscle cells.
title_sort micrornas dynamically remodel gastrointestinal smooth muscle cells
url http://europepmc.org/articles/PMC3077387?pdf=render
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