Alpha V integrin prolongs collagenase production through Jun activation binding protein 1.

Published

Journal Article

Robust expression of alphav integrin and matrix metalloproteinase 1 (MMP1) plays an important role in cancer metastasis and wound healing. A patient with an abnormal scar that appeared stretched and thinned out was found to have fibroblasts that overexpressed alphav integrin; therefore, a relationship between alphav integrin expression and MMP1 production was sought. A yeast 2 hybrid screen revealed alphav integrin interacts with jun activation binding domain-1 (JAB1). Mesenchymal-derived cells were transfected with the alphav integrin gene and incorporated into collagen lattices. Transfected cells maximally contracted collagen lattices beginning on day 5, whereas control transfected cells did not contract lattices. Late-phase collagen lattice contraction was inhibited by a pan-MMP inhibitor, BB4. Overexpression of alphav correlated with enhanced MMP1 transcription, as determined by a luciferase assay (P < or = 0.05). Diminution of JAB1 with JAB1 antisense abolished alphav integrin up-regulation of MMP1. We conclude alphav integrin signals through JAB1 to prolong MMP1 production and that this signaling pathway in fibroblasts may lead to abnormal scarring.

Full Text

Duke Authors

Cited Authors

  • Levinson, H; Sil, AK; Conwell, JE; Hopper, JE; Ehrlich, HP

Published Date

  • August 2004

Published In

Volume / Issue

  • 53 / 2

Start / End Page

  • 155 - 161

PubMed ID

  • 15269586

Pubmed Central ID

  • 15269586

International Standard Serial Number (ISSN)

  • 0148-7043

Digital Object Identifier (DOI)

  • 10.1097/01.sap.0000112281.97409.a6

Language

  • eng

Conference Location

  • United States