Hyaluronan is increased in hypertrophic scarring and has been shown to influence cellular differentiation. The hypothesis to be tested is that cutaneous fibroblasts are functionally heterogeneous and that trauma gives rise to abnormal scar fibroblasts with altered capacity to respond to TGF-b1 and PDGF.
The Specific Aims are to (1) determine whether the expression of TGF-b1 differs in fibroblasts derived from normal and abnormal orofacial scar tissues; (2) determine whether exogenous TGF-b1 produces differential activation of fibroblasts derived from normal vs. abnormal tissues by altering the expression of PDGF-alpha or -b receptors; and (3) examine whether TGF-b1 modulates the synthesis of either hyaluronan or hyaluronan receptors in fibroblasts derived from normal and abnormal scar tissues in an autocrine manner. The expression of TGF-b1 will be assayed in organ and cell cultures from normal and abnormal skin. The effects of TGF-b1 on PDGF receptors and CD44 (a hyaluronan receptor) mRNA and protein will be monitored by Northern blots, immunocytochemistry and radioimmunobinding. The effects of TGF-b1 on the synthesis of hyaluronan will also be monitored in cells using a radiolabeled hyaluronan precursor.
