SRF and miRs in smooth muscle differentiation and proliferation (WP1991)

Homo sapiens

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.


Samuel Sklar , Kathy Ivey , Alex Pico , Daniela Digles , Kristina Hanspers , Egon Willighagen , Martina Summer-Kutmon , Lauren J. Dupuis , and Eric Weitz


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Homo sapiens




Pathway Ontology

microRNA pathway microRNA pathway

Cell Type Ontology

smooth muscle cell neural crest derived smooth muscle myoblast


Label Type Compact URI Comment
CAMK2D GeneProduct ensembl:ENSG00000145349
MYOCD GeneProduct ensembl:ENSG00000141052
KLF4 GeneProduct ensembl:ENSG00000136826
SRF GeneProduct ncbigene:6722
MEF2D GeneProduct ensembl:ENSG00000116604
NKX2-5 GeneProduct ensembl:ENSG00000183072
CCND2 GeneProduct ensembl:ENSG00000118971
MYOCD GeneProduct ensembl:ENSG00000141052
ELK1 GeneProduct ensembl:ENSG00000126767
MEF2A GeneProduct ensembl:ENSG00000068305
KLF4 GeneProduct ensembl:ENSG00000136826
ELK1 GeneProduct ensembl:ENSG00000126767
SRF GeneProduct ncbigene:6722
SRF GeneProduct ncbigene:6722
MEF2B GeneProduct ensembl:ENSG00000213999
MEF2C GeneProduct ensembl:ENSG00000081189
SRF GeneProduct ncbigene:6722


  1. microRNA-133a regulates cardiomyocyte proliferation and suppresses smooth muscle gene expression in the heart. Liu N, Bezprozvannaya S, Williams AH, Qi X, Richardson JA, Bassel-Duby R, et al. Genes Dev. 2008 Dec 1;22(23):3242–54. PubMed Europe PMC Scholia
  2. miR-145 and miR-143 regulate smooth muscle cell fate and plasticity. Cordes KR, Sheehy NT, White MP, Berry EC, Morton SU, Muth AN, et al. Nature. 2009 Aug 6;460(7256):705–10. PubMed Europe PMC Scholia
  3. Serum response factor-dependent MicroRNAs regulate gastrointestinal smooth muscle cell phenotypes. Park C, Hennig GW, Sanders KM, Cho JH, Hatton WJ, Redelman D, et al. Gastroenterology. 2011 Jul;141(1):164–75. PubMed Europe PMC Scholia