The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Induction of MicroRNA-221 by Platelet-derived Growth Factor Signaling Is Critical for Modulation of Vascular Smooth Muscle Phenotype
Open accessAbstract
The platelet-derived growth factor (PDGF) signaling pathway is a critical regulator of animal development and homeostasis. Activation of the PDGF pathway leads to neointimal proliferative responses to artery injury; it promotes a switch of vascular smooth muscle cells (vSMC) to a less contractile phenotype by inhibiting the SMC-specific gene expression and increasing the rate of proliferation and migration. The molecular mechanism for these pleiotropic effects of PDGFs has not been fully described. Here, we identify the microRNA-221 (miR-221), a small noncoding RNA, as a modulator of the phenotypic change of vSMCs in response to PDGF signaling. We demonstrate that miR-221 is transcriptionally induced upon PDGF treatment in primary vSMCs, leading to down-regulation of the targets c-Kit and p27Kip1. Down-regulation of p27Kip1 by miR-221 is critical for PDGF-mediated induction of cell proliferation. Additionally, decreased c-Kit causes inhibition of SMC-specific contractile gene transcription by reducing the expression of Myocardin (Myocd), a potent SMC-specific nuclear coactivator. Our study demonstrates that PDGF signaling, by modulating the expression of miR-221, regulates two critical determinants of the vSMC phenotype; they are SMC gene expression and cell proliferation.
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Cites
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Widespread changes in protein synthesis induced by microRNAs
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CDK inhibitors: Cell cycle regulators and beyond
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Extensive modulation of a set of microRNAs in primary glioblastoma
Ciafrè, S. A., Galardi, S., Mangiola, A., Ferracin, M., Liu, C.-G., Sabatino, G., Negrini, M., Maira, G., Croce, C. M., & Farace, M. G. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.07.030 · Cited by 1,096
Role of microRNAs in vascular diseases, inflammation, and angiogenesis
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Cited by
Wang (2012) · doi:10.1161/circresaha.111.261388 · Cited by 957
Origin and differentiation of vascular smooth muscle cells
Wang, G., Jacquet, L., Karamariti, E., & Xu, Q. (2015) · The Journal of Physiology · doi:10.1113/jp270033 · Cited by 299
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Microarray based analysis of microRNA expression in rat cerebral cortex after traumatic brain injury
Lei, P., Li, Y., Chen, X., Yang, S., & Zhang, J. (2009) · Brain Research · doi:10.1016/j.brainres.2009.05.074 · Cited by 193
Metadata
- Authors
- Davis, B. N., Hilyard, A. C., Nguyen, P. H., Lagna, G., & Hata, A.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2009-02
- Volume
- 284
- Issue
- 6
- Pages
- 3728-3738
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2005406090
- Cited by
- 327
- References
- 7
- FWCI
- 7.08
- Type
- journal article
- Language
- en
- Open access
- hybrid
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