Expression of apoptosis-associated genes by human dermal scar fibroblasts

The purpose of this study was to determine if aberrant apoptosis plays a ro le in pathologic wound healing as manifested by hypertrophic scarring and k eloid formation. Apoptosis has recently been found to participate in the tr ansition between granulation tissue and the development of definitive scar. The question that remains to be answered is what stimuli initiate apoptosi s during wound healing. Hitherto, regulatory factors and pathways involved have been largely undefined. We investigated heterogeneity among fibroblast s derived from normal skin and keloid scar, by examining apoptotic profiles and pathways for these cells. Quantitative analysis of apoptotic cells usi ng an Annexin-V-FITC binding assay st-cowed that normal skin fibroblast cul tures were found to have a two-fold higher percentage of apoptotic cells th an did keloid fibroblast cultures. To study apoptotic pathways and related death-associated genes, a ribonuclease protection assay was performed for f ibroblasts exposed to anti-fas antibody and tumor necrosis factor-a to acti vate the Fas/TNF receptor apoptotic pathway. Compared with normal skin fibr oblasts, keloid fibroblasts exhibited decreased expression of apoptosis-ass ociated genes.