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Published on: February 15, 2022
Serum response factor-dependent MicroRNAs regulate gastrointestinal smooth muscle cell phenotypes.
Chanjae Park1, Grant W Hennig, Kenton M Sanders
1Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada, USA.
Gastroenterology
|April 9, 2011
Summary
Smooth muscle cells (SMCs) change phenotypes, regulated by serum response factor (SRF). This study identifies SRF-dependent microRNAs (miRNAs) controlling SMC phenotypes by targeting SRF and its cofactors.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- Smooth muscle cells (SMCs) exhibit phenotypic plasticity crucial in various pathophysiological states.
- Serum response factor (SRF) is a key transcription factor regulating SMC contractile genes via CArG box binding.
- MicroRNAs (miRNAs) are known regulators of SMC phenotype transitions, but their complete transcriptome and SRF-dependent regulation in SMCs remain uncharacterized.
Purpose of the Study:
- To comprehensively identify the microRNA transcriptome (miRNAome) of gastrointestinal (GI) smooth muscle cells (SMCs).
- To determine the regulatory role of serum response factor (SRF) in the SMC miRNAome.
- To identify specific SMC-phenotypic miRNAs and elucidate their regulatory targets.
Main Methods:
- Genome-wide identification of miRNA transcriptomes in mouse and human GI SMCs using massively parallel sequencing.
- Mapping of CArG boxes within miRNA genes and validation through SRF knockdown and microarrays.
- Quantitative polymerase chain reaction (qPCR) to identify SMC-phenotypic miRNAs in differentiated and proliferating SMCs.
- Bioinformatic analysis and target validation to confirm SRF-dependent miRNA regulation of SMC phenotype.
Main Results:
- Discovery of hundreds of conserved, unique miRNAs constituting the SM miRNAome in both species.
- Identification of numerous CArG boxes within the SM miRNAome, many exhibiting an SRF-dependent signature.
- Characterization of approximately 100 SMC-phenotypic miRNAs differentially expressed in differentiated or proliferative SMC states.
- Demonstration that SRF-dependent, SMC-phenotypic miRNAs directly regulate SRF, MYOCD, and ELK1 expression.
Conclusions:
- Gastrointestinal smooth muscle cell (SMC) phenotypes are orchestrated by SRF-dependent microRNAs (miRNAs).
- These identified miRNAs play a critical role in regulating the expression of key factors including SRF, MYOCD, and ELK1, thereby controlling SMC phenotype.
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