scholarly journals Molecular Control of Smooth Muscle Cell Differentiation Marker Genes by Serum Response Factor and Its Interacting Proteins

10.5772/36890 ◽  
2012 ◽  
Author(s):  
Tadashi Yoshida
Keyword(s):  
Smooth Muscle ◽  
Cell Differentiation ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Serum Response Factor ◽  
Marker Genes ◽  
Response Factor ◽  
Molecular Control ◽  
Differentiation Marker ◽  
Serum Response

scholarly journals Serum Response Factor–Dependent MicroRNAs Regulate Gastrointestinal Smooth Muscle Cell Phenotypes

2011 ◽  
Vol 141 (1) ◽  
pp. 164-175 ◽  
Author(s):  
Chanjae Park ◽  
Grant W. Hennig ◽  
Kenton M. Sanders ◽  
Jonathan H. Cho ◽  
William J. Hatton ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Serum Response Factor ◽  
Response Factor ◽  
Gastrointestinal Smooth Muscle ◽  
Cell Phenotypes ◽  
Serum Response

scholarly journals A serum response factor-dependent transcriptional regulatory program identifies distinct smooth muscle cell sublineages.

1997 ◽  
Vol 17 (4) ◽  
pp. 2266-2278 ◽  
Author(s):  
S Kim ◽  
H S Ip ◽  
M M Lu ◽  
C Clendenin ◽  
M S Parmacek
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Transgenic Mice ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Promoter Activity ◽  
Serum Response Factor ◽  
Response Factor ◽  
Transcriptional Regulatory ◽  
Serum Response

The SM22alpha promoter has been used as a model system to define the molecular mechanisms that regulate smooth muscle cell (SMC) specific gene expression during mammalian development. The SM22alpha gene is expressed exclusively in vascular and visceral SMCs during postnatal development and is transiently expressed in the heart and somites during embryogenesis. Analysis of the SM22alpha promoter in transgenic mice revealed that 280 bp of 5' flanking sequence is sufficient to restrict expression of the lacZ reporter gene to arterial SMCs and the myotomal component of the somites. DNase I footprint and electrophoretic mobility shift analyses revealed that the SM22alpha promoter contains six nuclear protein binding sites (designated smooth muscle elements [SMEs] -1 to -6, respectively), two of which bind serum response factor (SRF) (SME-1 and SME-4). Mutational analyses demonstrated that a two-nucleotide substitution that selectively eliminates SRF binding to SME-4 decreases SM22alpha promoter activity in arterial SMCs by approximately 90%. Moreover, mutations that abolish binding of SRF to SME-1 and SME-4 or mutations that eliminate each SME-3 binding activity totally abolished SM22alpha promoter activity in the arterial SMCs and somites of transgenic mice. Finally, we have shown that a multimerized copy of SME-4 (bp -190 to -110) when linked to the minimal SM22alpha promoter (bp -90 to +41) is necessary and sufficient to direct high-level transcription in an SMC lineage-restricted fashion. Taken together, these data demonstrate that distinct transcriptional regulatory programs control SM22alpha gene expression in arterial versus visceral SMCs. Moreover, these data are consistent with a model in which combinatorial interactions between SRF and other transcription factors that bind to SME-4 (and that bind directly to SRF) activate transcription of the SM22alpha gene in arterial SMCs.

scholarly journals Smooth Muscle Cell Genome Browser: Enabling the Identification of Novel Serum Response Factor Target Genes

PLoS ONE ◽  
2015 ◽  
Vol 10 (8) ◽  
pp. e0133751 ◽  
Author(s):  
Moon Young Lee ◽  
Chanjae Park ◽  
Robyn M. Berent ◽  
Paul J. Park ◽  
Robert Fuchs ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Target Genes ◽  
Serum Response Factor ◽  
Genome Browser ◽  
Response Factor ◽  
Cell Genome ◽  
Serum Response

scholarly journals Smooth Muscle Cell–Enriched Long Noncoding RNA Regulates Cell Plasticity and Atherosclerosis by Interacting With Serum Response Factor

2021 ◽  
Author(s):  
Huaner Ni ◽  
Stefan Haemmig ◽  
Yihuan Deng ◽  
Jingshu Chen ◽  
Viorel Simion ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Noncoding Rna ◽  
Serum Response Factor ◽  
Mass Spectrometry Analysis ◽  
Response Factor ◽  
Dependent Manner ◽  
Serum Response

Objective: Vascular smooth muscle cell (VSMC) plasticity plays a critical role in the development of atherosclerosis. Long noncoding RNAs (lncRNAs) are emerging as important regulators in the vessel wall and impact cellular function through diverse interactors. However, the role of lncRNAs in regulating VSMCs plasticity and atherosclerosis remains unclear. Approach and Results: We identified a VSMC-enriched lncRNA cardiac mesoderm enhancer-associated noncoding RNA (CARMN) that is dynamically regulated with progression of atherosclerosis. In both mouse and human atherosclerotic plaques, CARMN colocalized with VSMCs and was expressed in the nucleus. Knockdown of CARMN using antisense oligonucleotides in Ldlr −/− mice significantly reduced atherosclerotic lesion formation by 38% and suppressed VSMCs proliferation by 45% without affecting apoptosis. In vitro CARMN gain- and loss-of-function studies verified effects on VSMC proliferation, migration, and differentiation. TGF-β1 (transforming growth factor-beta) induced CARMN expression in a Smad2/3-dependent manner. CARMN regulated VSMC plasticity independent of the miR143/145 cluster, which is located in close proximity to the CARMN locus. Mechanistically, lncRNA pulldown in combination with mass spectrometry analysis showed that the nuclear-localized CARMN interacted with SRF (serum response factor) through a specific 600–1197 nucleotide domain. CARMN enhanced SRF occupancy on the promoter regions of its downstream VSMC targets. Finally, knockdown of SRF abolished the regulatory role of CARMN in VSMC plasticity. Conclusions: The lncRNA CARMN is a critical regulator of VSMC plasticity and atherosclerosis. These findings highlight the role of a lncRNA in SRF-dependent signaling and provide implications for a range of chronic vascular occlusive disease states.

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