Defining the Role of Integrin Alpha 11 in Wound Healing and Fibrosis
Final rept. 1 Sep 2008-30 Aug 2010
SYNEDGEN INC CLAREMONT CA
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Integrin alpha 11 Itga11 is the most recently identified integrin subunit and has been associated with fibrotic disease. To investigate the role of Itga11 in fibroblast behavior in wound healing and fibrosis we used Itga11 null mice. We have found that fibroblasts lacking Itga11 KO repair a scratch in a confluent monolayer faster than their normal Het counterparts, and show increased proliferation along the margins of the scratch. In an attached collagen matrix model of fibrosis the KO fibroblasts show decreased expression of Col1A1 and alphaSMA, two markers of activated fibroblasts. However we did not find altered expression of these genes in a healing wound. In attached collagen gels KO fibroblasts exhibit decreased MMP13 collagenase activity, and in healing wounds blood vessels are abnormally distributed. Taken together these data suggest that Itga11 is involved in remodeling of the extracellular matrix and is required for the developing blood vessels to penetrate the wound bed.
- Medicine and Medical Research