Data di Pubblicazione:
2003
Citazione:
Regulation of extracellular matrix remodeling by smooth muscle cells / E. Raines, N. Ferri. - In: ATHEROSCLEROSIS SUPPLEMENTS. - ISSN 1567-5688. - 4:2(2003), pp. 13-13. (Intervento presentato al 13. convegno 13th International Symposium on Atherosclerosis tenutosi a KYOTO, JAPAN nel 2003) [10.1016/S1567-5688(03)90052-3].
Abstract:
Although remodeling of vessels can dramatically alter lumen diameter and
clinical sequelae, the molecular mechanisms regulating extracellular matrix
turnover and remodeling are still not well understood. In vitro studies have
suggested that adhesive events strongly regulate fibroblast contraction and
expression of matrix metalloproteinases (MMPs). To investigate remodeling
and contraction in human smooth muscle (SMC), we have compared their culture
on monomer and polymerized collagen gels, conditions that mimic some
of the features of injured and normal vessels, respectively. We demonstrate
that polymerized collagen activates the transcriptional factor NF-kappaB in
human aortic SMC and that NF-kappaB induction of MMP1 and α2 integrin
is required for collagen degradation and contraction. Overexpression of either
of these two NF-kappaB gene products can rescue blockade of collagen gel
contraction by overexpression of the NF-kappaB inhibitor IkappaBα. MMP2
activation is also induced by polymerized collagen, but is independent of
NF-kappaB transcriptional activation. The pericellular activation of MMP-2
is particularly enhanced by the Discoidin Receptor-2 (DDR-2), a recently
identified tyrosine kinase receptor for collagen expressed on SMC in culture
and in lesions of atherosclerosis. Polymerized collagen-induced activation
of MMP-2 is independent of DDR2 tyrosine phosphorylation, but requires
portions of the DDR2 cytoplasmic domain. Our data provide evidence for a
central role for NF-kappaB gene products and DDR2 in the tightly regulated
process of SMC remodeling of the extracellular matrix.
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
E. Raines, N. Ferri
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