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

Homo sapiens

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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.

Authors

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

Activity

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Organisms

Homo sapiens

Communities

ExRNA

Annotations

Pathway Ontology

microRNA pathway microRNA pathway

Cell Type Ontology

smooth muscle cell neural crest derived smooth muscle myoblast

Participants
Query Drugst.One

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
ELK1 GeneProduct ensembl:ENSG00000126767
MEF2A GeneProduct ensembl:ENSG00000068305
MEF2B GeneProduct ensembl:ENSG00000213999
MEF2C GeneProduct ensembl:ENSG00000081189

References

  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