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  • Whitley Vistisen posted an update 4 months, 1 week ago

    MTMMP, which is induced by phorbol esters, may have an AP site within its promoter, although no sequence data have been published. . GLA mRNA expression by fibroblasts within collagen lattices.Adult palmar fibroblasts were cultured within mechanically relaxed collagen lattices.After probing for GLA message, blots were stripped, then reprobed for GAPDH expression.GLA mRNA level was decreased in stabilized collagen lattices compared with floating or released collagen lattices.Adult palmar fibroblasts were cultured on tissue culture plates, then incubated with or without M cyto D in serumfree medium for h.In addition, levels of GLA mRNA increased in mechanically relaxed compared to mechanically stressed collagen lattices.These results suggest that as cells lose mechanical stress they regulate GLA activation by increasing the expression of MTMMP, as well as increasing the expression of GLA.While it has been proposed that the threedimensional organization of the collagen matrix, as well as cell binding to collagen, regulates GLA activation, we found that mechanical stress, and not matrix organization, may regulate this activation.Mechanically stressed collagen lattices, when compared with mechanically relaxed lattices, showed a marked reduction in GLA activation and MTMMP expression, even though fibroblasts were surrounded by a threedimensional collagen matrix in both cases.Thus, the mechanism by which mechanical stress and actin organization regulates transcription of GLA may be different from that proposed for MTMMP.Mechanical forces may play an important role in regulating the expression and assembly of ECM macromolecules, as well as an increase in the expression of type I collagen. These results have led to the proposal that mechanical stress induces a matrixdepositing fibroblast phenotype. Our results demonstrating that mechanical stress results in decreased activation of GLA are consistent with this proposal.Interstitial collagenase, as well as plasminogen activators, may be similarly regulated by mechanical stress. These results suggest that, opposite to the matrixdepositing phenotype promoted by mechanical stress, a mechanically relaxed environment may promote a proteolytic phenotype favoring matrix turnover.Thus, the mechanical forces described here in the in vitro collagen lattice models may also play an important role in vivo during wound healing and pathological contractures.Fibroblasts in granulation tissue exert Vitamin D2 tension on the ECM, develop stress, and contract the matrix, thereby bringing the wound margins closer together. Once the wound defect is closed by a combination of contraction and new matrix synthesis, the fibroblast population regresses and ECM remodeling begins.Our studies suggest that, while the wound is under tension and depositing a new ECM, little MMP activity would be present.Once the new matrix replaces the wound and the tissue becomes mechanically relaxed, MMP expression and activation would occur, promoting ECM remodeling.Consistent with this proposal is the observation that increased skin tension contributes to increased scarring after surgery. Vu, Rose W. Liu and Eric W. Howard J. Biol. Chem. doi. jbc. Access the most updated version of this article at http:www.jbc.orgcontent When a correction for this article is posted Click here to choose from all of JBCs email alerts This article cites references, of which can be accessed free at http:www.jbc.orgcontent.full.htmlreflist Downloadedfromhttp: http://www.jbc.orgbyguestonAugust, Here, we demonstrate that MSS is a lipid kinase.