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Cited by 1,585MicroRNA in disease regulationCongenital heart defects researchDevelopmental Biology and Gene Regulation

miR-145 and miR-143 regulate smooth muscle cell fate and plasticity

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Cordes, Kimberly R., Sheehy, Neil T., White, Mark P., Berry, Emily C., Morton, Sarah U., Muth, Alecia N., Lee, Ting-Hein, Miano, Joseph M. +2 more·2009·Nature
DOI 10.1038/nature08195PMC PMC2769203
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Abstract

MicroRNAs (miRNAs) are regulators of myriad cellular events, but evidence for a single miRNA that can efficiently differentiate multipotent stem cells into a specific lineage or regulate direct reprogramming of cells into an alternative cell fate has been elusive. Here we show that miR-145 and miR-143 are co-transcribed in multipotent murine cardiac progenitors before becoming localized to smooth muscle cells, including neural crest stem-cell-derived vascular smooth muscle cells. miR-145 and miR-143 were direct transcriptional targets of serum response factor, myocardin and Nkx2-5 (NK2 transcription factor related, locus 5) and were downregulated in injured or atherosclerotic vessels containing proliferating, less differentiated smooth muscle cells. miR-145 was necessary for myocardin-induced reprogramming of adult fibroblasts into smooth muscle cells and sufficient to induce differentiation of multipotent neural crest stem cells into vascular smooth muscle. Furthermore, miR-145 and miR-143 cooperatively targeted a network of transcription factors, including Klf4 (Kruppel-like factor 4), myocardin and Elk-1 (ELK1, member of ETS oncogene family), to promote differentiation and repress proliferation of smooth muscle cells. These findings demonstrate that miR-145 can direct the smooth muscle fate and that miR-145 and miR-143 function to regulate the quiescent versus proliferative phenotype of smooth muscle cells.

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  • miR-145 positively regulates myocardin and its expression is decreased in atherosclerotic lesions.

    “It was shown that expression of miR-145, which positively regulates myocardin, is decreased in atherosclerotic lesions (Table 6) [276].”

    From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [276]

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Authors
Cordes, K. R., Sheehy, N. T., White, M. P., Berry, E. C., Morton, S. U., Muth, A. N., Lee, T.-H., Miano, J. M., Ivey, K. N., & Srivastava, D.
Affiliations
  • Gladstone Institutes (US)
  • University of Rochester Medicine (US)
Corresponding author
Srivastava, Deepak
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2009-07-05
Volume
460
Issue
7256
Pages
705-710
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature08195
PMC
PMC2769203
OpenAlex
W1996630410
Cited by
1,585
References
2
Citations by year
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FWCI
39.60
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • American Heart Association
  • Gladstone Institutes
  • National Institutes of Health (1c06rr018928-01)
  • National Heart, Lung, and Blood Institute (R01HL132574, HL-091168, HL 62572, R01HL062572, R01HL091168)
  • National Center for Research Resources (C06-RR-018928)
  • Core Research for Evolutional Science and Technology
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
miR-145, miR-143, microRNA, vascular smooth muscle cells, neural crest stem cells, cardiac progenitor cells, myocardin, Nkx2.5, serum response factor, cell differentiation, cell proliferation, KLF4, Elk-1, atherosclerosis
MeSH terms
Homeobox Protein Nkx-2.5, Kruppel-Like Factor 4, Animals, Cell Differentiation, Female, Gene Expression Regulation, Male, Mice, Transgenic, Models, Biological, Myocardium, Transcription Factors, Transcription, Genetic, Vascular Diseases, Homeodomain Proteins, Cell Lineage, Myocytes, Smooth Muscle, MicroRNAs, Cell Proliferation, ets-Domain Protein Elk-4, Mice

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