SRF and miRs in Smooth Muscle Differentiation and Proliferation (Homo sapiens)

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33333311333233213323232Mechanism UnknownNucleusMEF2DSmooth Muscle DifferentiationMIR133A1MIR133A2MYOCDMIR145KLF4MIR143CAMK2DMYOCDMEF2AMIR199A1CCND2SRFNKX2-5MIR214ELK1Smooth Muscle ProliferationKLF4ELK1SRFSRF3MEF2BMEF2CSRF1Cytoplasm


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



  1. 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
  2. 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
  3. 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


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103014view15:25, 31 January 2019L DupuisUpdated microRNA genes from RNA to GeneProduct
103012view15:23, 31 January 2019L DupuisUpdated microRNA genes from RNA to GeneProduct
89637view06:12, 22 September 2016EgonwConnected lines.
86848view14:55, 13 July 2016MkutmonOntology Term : 'microRNA pathway' added !
86842view13:38, 13 July 2016MkutmonOntology Term : 'PW:0000808' removed !
82940view08:57, 14 November 2015EgonwUpdated Ensembl identifiers.
75261view21:21, 13 May 2014Khanspersupdated layout, changed miRNA data nodes to RNA type
75260view21:20, 13 May 2014Khanspers
74458view00:09, 23 April 2014AlexanderPicofixed typo
68900view17:29, 8 July 2013MaintBotUpdated to 2013 gpml schema
67654view11:45, 26 June 2013DdiglesOntology Term : 'microRNA pathway' added !
59103view22:15, 21 February 2013MaintBotUpdated Ensembl and UniProt data source
43330view20:04, 14 June 2011AlexanderPicoOntology Term : 'miRNA pathway' added !
43329view20:03, 14 June 2011AlexanderPicoOntology Term : 'smooth muscle myoblast' added !
43328view20:02, 14 June 2011AlexanderPicoOntology Term : 'smooth muscle cell neural crest derived' added !
43239view00:19, 9 June 2011KathyIveyModified description
43238view00:11, 9 June 2011KathyIveyPeriodical save, work in progress
43237view00:00, 9 June 2011KathyIveyPeriodical save, work in progress
43118view22:00, 2 June 2011Samuel Sklarcyroplasm
43117view21:16, 2 June 2011Samuel SklarSpecify description
42997view21:05, 25 May 2011Samuel SklarModified categories
42996view21:00, 25 May 2011Samuel SklarSpecify description
42995view20:58, 25 May 2011Samuel SklarSpecify description
42994view20:51, 25 May 2011Samuel SklarPeriodical save, work in progress
42991view18:24, 25 May 2011Samuel SklarSpecify description
42990view18:18, 25 May 2011Samuel SklarNew pathway

External references


View all...
NameTypeDatabase referenceComment
CAMK2DGeneProductENSG00000145349 (Ensembl)
CCND2GeneProductENSG00000118971 (Ensembl)
ELK1GeneProductENSG00000126767 (Ensembl)
KLF4GeneProductENSG00000136826 (Ensembl)
MEF2AGeneProductENSG00000068305 (Ensembl)
MEF2BGeneProductENSG00000213999 (Ensembl)
MEF2CGeneProductENSG00000081189 (Ensembl)
MEF2DGeneProductENSG00000116604 (Ensembl)
MIR133A1RnaENSG00000207786 (Ensembl)
MIR133A2RnaENSG00000207764 (Ensembl)
MIR143RnaENSG00000208035 (Ensembl)
MIR145GeneProductENSG00000207700 (Ensembl)
MIR199A1RnaENSG00000207752 (Ensembl)
MIR214RnaENSG00000207949 (Ensembl)
MYOCDGeneProductENSG00000141052 (Ensembl)
NKX2-5GeneProductENSG00000183072 (Ensembl)
SRFGeneProduct6722 (Entrez Gene)
Smooth Muscle DifferentiationPathway
Smooth Muscle ProliferationPathway

Annotated Interactions

No annotated interactions

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