title: miR-15b induced by platelet-derived growth factor signaling is required for vascular smooth muscle cell proliferation.
abstract: The platelet-derived growth factor (PDGF) signaling pathway is essential for inducing a dedifferentiated state of vascular smooth muscle cells (VSMCs). Activation of PDGF inhibits smooth muscle cell (SMC)-specific gene expression and increases the rate of proliferation and migration, leading to dedifferentiation of VSMCs. Recently, microRNAs have been shown to play a critical role in the modulation of the VSMC phenotype in response to extracellular signals. However, little is known about microRNAs regulated by PDGF in VSMCs. Herein, we identify microRNA-15b (miR-15b) as a mediator of VSMC phenotype regulation upon PDGF signaling. We demonstrate that miR-15b is induced by PDGF in pulmonary artery smooth muscle cells and is critical for PDGF-mediated repression of SMC-specific genes. In addition, we show that miR-15b promotes cell proliferation. These results indicate that PDGF signaling regulates SMC-specific gene expression and cell proliferation by modulating the expression of miR-15b to induce a dedifferentiated state in the VSMCs.
authors.affiliation: Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 406-772, Korea harakang@incheon.ac.kr.
authors.forename: Sunghwan
authors.initials: S
authors.lastname: Kim
authors.forename: Hara
authors.initials: H
authors.lastname: Kang
mesh_terms: D000077214:Becaplermin; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology*; D012342:RNA, Small Nuclear / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C505361:MIRN15 microRNA, human; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; D020574:Proto-Oncogene Proteins c-sis; D012342:RNA, Small Nuclear; C405486:U6 small nuclear RNA; D000077214:Becaplermin