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 language | English |
|---|---|
| Pages (from-to) | 19757-19764 |
| Number of pages | 8 |
| Journal | Journal of Biological Chemistry |
| Volume | 278 |
| Issue number | 22 |
| DOIs | |
| Publication status | Published - May 30 2003 |
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ASJC Scopus subject areas
- Biochemistry
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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 journal › Article
}
TY - JOUR
T1 - An NF-κB-dependent transcriptional program is required for collagen remodeling by human smooth muscle cells
AU - Ferri, Nicola
AU - Garton, Kyle J.
AU - Raines, Elaine W.
PY - 2003/5/30
Y1 - 2003/5/30
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M212714200
DO - 10.1074/jbc.M212714200
M3 - Article
C2 - 12649281
AN - SCOPUS:0037827712
VL - 278
SP - 19757
EP - 19764
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 22
ER -