POMC and fibroblast biology.

Abstract

We evidenced in vitro proopiomelanocortin (POMC) mRNA-transcription in human dermal fibroblasts using Northern blot hybridization. Modulation of POMC gene expression by cytokines (transforming growth factor-beta, TGF-beta, and tumor necrosis factor-alpha, TNF-alpha) was investigated by incubating human normal fibroblasts with 1 and 10 ng/ml cytokines, either alone or in combination, for 24 hours. Our results show that dermal fibroblasts express POMC at significant levels under unstimulated conditions. POMC steady-state levels were significantly reduced by addition of TGF-beta. On the other hand, TNF-alpha exerted a stimulatory effect on POMC mRNA transcription, partially counteracting the effect of TGF-beta. These data provide the first demonstration of POMC gene expression in cultured skin fibroblasts. The opposite regulatory effect of TGF-beta and TNF-alpha, two cytokines primarily involved in extracellular matrix regulation, suggests a possible role for POMC-derived peptides in fibroblast activity. We also investigated POMC mRNA expression in keloid-derived fibroblasts in culture, and its regulation by TGF-beta added at the highest concentration documented for inhibition. Keloid-derived fibroblasts showed clearly detectable levels of POMC mRNA in basal conditions, and no alteration of POMC gene expression was observed when TGF-beta was added in culture. The altered TGF-beta regulation of POMC mRNA levels suggest that POMC-derived peptides may play a role in the pathogenesis of keloid formation through an autocrine/paracrine network, resulting in modulation of extracellular matrix synthesis.