An NF-κB-dependent transcriptional program is required for collagen remodeling by human smooth muscle cells

Nicola Ferri, Kyle J. Garton, Elaine W. Raines

Research output: Contribution to journalArticle

34 Citations (Scopus)

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. To investigate these processes in human smooth muscle, 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 show that culture on polymerized, but not monomer, collagen leads to the activation of the transcription factor NF-κB through phosphorylation and degradation of its inhibitor, IκBα. Coincident with NF-κB activation, expression of MMP1, MMP2, and α2 integrin increases on polymerized collagen. Specific inhibition of NF-κB by retroviral overexpression of wild-type IκBα or phosphorylation-resistant, IκBα-stabilized mutant (IκBαSer32,36/Ala) reverses the increases in MMP1 and α2β1 on polymerized collagen and decreases collagen gel contraction and degradation. However, forced overexpression of α2β1 integrin or MMP1 in smooth muscle cells expressing IκBαSer32,36/Ala rescues their ability to contract collagen gels. Thus, polymerized collagen induces NF-κB-dependent expression of MMP1 and α2β1 integrin, that are required for smooth muscle extracellular matrix remodeling.

Original languageEnglish
Pages (from-to)19757-19764
Number of pages8
JournalJournal of Biological Chemistry
Volume278
Issue number22
DOIs
Publication statusPublished - May 30 2003

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Smooth Muscle Myocytes
Muscle
Collagen
Cells
Integrins
Phosphorylation
Gels
Extracellular Matrix
Smooth Muscle
Monomers
Chemical activation
Degradation
Corrosion inhibitors
Transcription Factors

ASJC Scopus subject areas

  • Biochemistry

Cite this

An NF-κB-dependent transcriptional program is required for collagen remodeling by human smooth muscle cells. / Ferri, Nicola; Garton, Kyle J.; Raines, Elaine W.

In: Journal of Biological Chemistry, Vol. 278, No. 22, 30.05.2003, p. 19757-19764.

Research output: Contribution to journalArticle

Ferri, Nicola ; Garton, Kyle J. ; Raines, Elaine W. / An NF-κB-dependent transcriptional program is required for collagen remodeling by human smooth muscle cells. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 22. pp. 19757-19764.
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