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

Robust expression of av 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 over-expressed av integrin; therefore, a relationship between av integrin expression and MMP1 production was sought. A yeast 2 hybrid screen revealed av integrin interacts with jun activation binding domain-1 (JAB1). Mesenchymal-derived cells were transfected with the av 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 av correlated with enhanced MMP1 transcription, as determined by a luciferase assay (P ≤ 0.05). Diminution of JAB1 with JABI antisense abolished av integrin up-regulation of MMP1. We conclude av integrin signals through JAB1 to prolong MMP1 production and that this signaling pathway in fibroblasts may lead to abnormal scarring.