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. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
National Research Service Awards for Senior Fellows (F33)
Project #
5F33AR052241-02
Application #
7008589
Study Section
Special Emphasis Panel (ZRG1-F10 (20))
Program Officer
Lapham, Cheryl K
Project Start
2005-01-01
Project End
2007-12-31
Budget Start
2006-01-01
Budget End
2007-12-31
Support Year
2
Fiscal Year
2006
Total Cost
$61,076
Indirect Cost
Name
Middle Tennessee Research Institute
Department
Type
DUNS #
111010943
City
Nashville
State
TN
Country
United States
Zip Code
37212
Russell, Shirley B; Smith, Joan C; Huang, Minjun et al. (2015) Pleiotropic Effects of Immune Responses Explain Variation in the Prevalence of Fibroproliferative Diseases. PLoS Genet 11:e1005568
Velez Edwards, Digna R; Tsosie, Krystal S; Williams, Scott M et al. (2014) Admixture mapping identifies a locus at 15q21.2-22.3 associated with keloid formation in African Americans. Hum Genet 133:1513-23
Russell, Shirley B; Russell, James D; Trupin, Kathryn M et al. (2010) Epigenetically altered wound healing in keloid fibroblasts. J Invest Dermatol 130:2489-96
Smith, Joan C; Boone, Braden E; Opalenik, Susan R et al. (2008) Gene profiling of keloid fibroblasts shows altered expression in multiple fibrosis-associated pathways. J Invest Dermatol 128:1298-310