Gene Expression and Variation in Keloid Fibroblasts

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DESCRIPTION (provided by applicant): Our hypothesis is that fibroblasts from keloids and other fibroproliferative diseases that disproportionately affect individuals of African ancestry exhibit an altered pattern of gene expression that predisposes them to fibrosis. Microarray analysis will be used to identify a spectrum of genes that shows altered expression in keloid fibroblasts. Analysis of differentially expressed genes will be used to generate hypotheses concerning involvement of these genes in our previously reported differences in growth and matrix synthesis in response to glucocorticoids, phorbol ester tumor promoters, and TGF-beta, and to test the hypothesis that the disproportionately high occurrence of fibrosis in the population involves altered production and/or response to Th2 cytokines. Analysis of polymorphisms in genes that are likely to play roles in TGF-beta, glucocorticoid, and Th2 cytokine pathways will be used to examine possible associations between particular sequences and fibrosis in individuals of African ancestry. Future linkage studies based on our findings will be aimed at identifying cis- and trans-acting genes that create a susceptibility to fibrosis.