Purpose: Robust expression of av integrin in scar fibroblasts is associated with abnormal wound healing marked by atrophic, disrupted scar. A relationship between av integrin overexpression and collagenase expression was sought. The signaling pathway that mediates av integrin stimulated collagenase expression was investigated. Methods: Human Osteosarcoma Cells were transfected with the av integrin gene (HOSav cells). Overexpressing av integrin clones were incorporated into collagen lattices and a collagenase inhibitor added. A cDNA construct composed of the collagenase gene promoter fused to a luciferase reporter was transfected into HOS cells and cell lysates were analyzed. In addition, a screen was used to detect potential av integrin signaling molecules. HOS cells were transfected with Jun activation binding domain-1 (JAB1) antisense and the collagenase luciferase reporter and cell lysates were assayed for luciferase activity. Results: HOS cells did not contract collagen lattices but HOSav cells contracted collagen lattices beginning on day six. Blockade of collagenase inhibited av mediated lattice contraction. Overexpressing HOS av cells expressed more collagenase. Downregulation of JAB1 blocked collagenase expression in HOS av cells. Discussion: Expression of av integrin is associated with enhanced collagenase production and thus, upregulation of av integrin may lead to scar breakdown. JAB1 mediates av integrin signaling to stimulate collagenase expression. JAB1 is a potential target for controlling scar remodeling.
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