Gremlin promotes vascular smooth muscle cell proliferation and migration

Gremlin promotes vascular smooth muscle cell proliferation and migration

Author Maciel, Thiago T. Autor UNIFESP Google Scholar
Melo, Rosilene S. Autor UNIFESP Google Scholar
Schor, Nestor Autor UNIFESP Google Scholar
Campos, Alexandre H. Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Albert Einstein Res & Educ Inst
Abstract Recent reports highlight the importance of BMP in the vasculature. We investigated the expression pattern and role of the BNIP antagonist gremlin in VSMC. We detected gremlin mRNA constitutive expression in adult and embryonic rat aortic VSMC, and in rat carotids. in vitro analysis demonstrated that angiotensin II, TGF-beta 1 and PDGF induced significant changes in gremlin mRNA expression. Gremlin stable overexpression in A7r5 cells blocked BMP signaling. BMP-mduced reduction in VSMC DNA synthesis was markedly inhibited by gremlin overexpression. in fact, gremlin overexpression increased DNA synthesis and cell counts, and accelerated cell cycle progression of VSMC, through mechanisms that include p27(kip1) down-regulation. Gremlin also led to marked increments in VSMC migration. in addition, gremlin gene silencing promoted a significant blockade on cell proliferation and migration. in vivo studies disclosed increased gremlin protein expression in the neointima of balloon-injured carotid arteries. in summary, the BMP antagonist gremlin is constitutively expressed in the normal vasculature. Gremlin induces VSMC proliferation and migration and is significantly regulated by growth factors and injury. We postulate that gremlin plays a part in the development of pathological phenotypic changes of adult VSMC. (c) 2007 Elsevier Inc. All rights reserved.
Keywords gremlin
bone morphogenetic proteins
vascular smooth muscle cell
proliferation
restenosis
Language English
Date 2008-02-01
Published in Journal of Molecular and Cellular Cardiology. London: Academic Press Ltd- Elsevier B.V., v. 44, n. 2, p. 370-379, 2008.
ISSN 0022-2828 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 370-379
Origin http://dx.doi.org/10.1016/j.yjmcc.2007.10.021
Access rights Closed access
Type Article
Web of Science ID WOS:000254043300017
URI http://repositorio.unifesp.br/handle/11600/30432

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