SRF and miRs in smooth muscle differentiation and proliferation (Homo sapiens)
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Description
Smooth muscle cells exhibit a unique plasticity, in that they are able to oscillate between proliferative and more quiescent, differentiated states. These two states are determined, in part, by a network of transcription factors, including Klf-4, Elk-1 and serum response factor (SRF), that regulate expression of genes controlling smooth muscle cell status. Two smooth muscle-enriched, co-transcribed microRNAs (miRNAs), miR-143 and miR-145, cooperatively target this transcription factor network to promote smooth muscle cell differentiation. miR-145 also acts in a positive feed-foward regulatory loop to enhance expression of the smooth muscle regulator, Myocardin (Myocd), which cooperates with SRF to activate transcription of miR-143/145. Conversely, the cardiac and skeletal muscle-enriched miRNA, miR-133, which is also under transcriptional control of both SRF and Mef2C, acts in a negative feed-back loop to decrease SRF translation. Other miRNAs, including miR-214 and miR-199a, also target SRF, limiting its activity in specific cell types.
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Ontology Terms
Bibliography
- Park C, Hennig GW, Sanders KM, Cho JH, Hatton WJ, Redelman D, Park JK, Ward SM, Miano JM, Yan W, Ro S; ''SRF-Dependent microRNAs Regulate Gastrointestinal Smooth Muscle Cell Phenotypes.''; Gastroenterology, 2011 PubMed Europe PMC Scholia
- Liu N, Bezprozvannaya S, Williams AH, Qi X, Richardson JA, Bassel-Duby R, Olson EN; ''microRNA-133a regulates cardiomyocyte proliferation and suppresses smooth muscle gene expression in the heart.''; Genes Dev, 2008 PubMed Europe PMC Scholia
- Cordes KR, Sheehy NT, White MP, Berry EC, Morton SU, Muth AN, Lee TH, Miano JM, Ivey KN, Srivastava D; ''miR-145 and miR-143 regulate smooth muscle cell fate and plasticity.''; Nature, 2009 PubMed Europe PMC Scholia
History
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External references
DataNodes
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Name | Type | Database reference | Comment |
---|---|---|---|
CAMK2D | GeneProduct | ENSG00000145349 (Ensembl) | |
CCND2 | GeneProduct | ENSG00000118971 (Ensembl) | |
ELK1 | GeneProduct | ENSG00000126767 (Ensembl) | |
KLF4 | GeneProduct | ENSG00000136826 (Ensembl) | |
MEF2A | GeneProduct | ENSG00000068305 (Ensembl) | |
MEF2B | GeneProduct | ENSG00000213999 (Ensembl) | |
MEF2C | GeneProduct | ENSG00000081189 (Ensembl) | |
MEF2D | GeneProduct | ENSG00000116604 (Ensembl) | |
MIR133A1 | Rna | ENSG00000276792 (Ensembl) | |
MIR133A2 | Rna | ENSG00000207764 (Ensembl) | |
MIR143 | Rna | ENSG00000208035 (Ensembl) | |
MIR145 | Rna | ENSG00000276365 (Ensembl) | |
MIR199A1 | Rna | ENSG00000207752 (Ensembl) | |
MIR214 | Rna | ENSG00000207949 (Ensembl) | |
MYOCD | GeneProduct | ENSG00000141052 (Ensembl) | |
NKX2-5 | GeneProduct | ENSG00000183072 (Ensembl) | |
SRF | GeneProduct | 6722 (Entrez Gene) | |
Smooth Muscle Differentiation | Pathway | ||
Smooth Muscle Proliferation | Pathway |
Annotated Interactions
No annotated interactions