Propiomelanocortin (POMC) gene expression by normal skin and keloid fibroblasts in culture: modulation by cytokines.
Originally described as a product of the pituitary gland, propiomelanocortin (POMC) has recently been identified in other tissues, such as in human skin, where it may accumulate in response to various stimuli. Thus far, epidermal keratinocytes, as well as melanocytes and macrophages, have been shown to express POMC. This study investigated the expression of POMC mRNA in cultured dermal fibroblasts derived from either normal skin or keloids. Using Northern blot hybridization with a POMC cDNA generated by RT-PCR of mRNA isolated from cardiac muscle, we demonstrated that dermal fibroblasts express POMC, as significant levels of mRNA were detected in unstimulated cells in culture. POMC transcript steady-state levels were strongly reduced by transforming growth factor-beta (TGF-beta), whereas tumor necrosis factor-alpha (TNF-alpha) counteracted the effect of TGF-beta and exerted a stimulatory activity on POMC mRNA levels. Reduction of POMC transcript levels by TGF-beta was also observed in cultured keratinocytes. Clearly detectable levels of POMC mRNA were detected in cultured keloid-derived fibroblasts; however, little, if any, regulation by TGF-beta was observed. These data represent the first demonstration of POMC expression by fibroblasts and down-regulation by TGF-beta. Furthermore, our results indicate altered TGF-beta regulation of POMC gene expression in keloid-derived fibroblasts, suggesting that POMC may play a role in the pathogenesis of keloid formation.
Teofoli
P
P
Department of Dermatology and Cutaneous Biology, Jefferson Medical College, Philadelphia, PA 19107, USA.
Motoki
K
K
Lotti
T M
TM
Uitto
J
J
Mauviel
A
A
D002478:Cells, Cultured; D015342:DNA Probes; D018076:DNA, Complementary / Q000235:genetics; D000078404:Epidermal Cells; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007627:Keloid / Q000473:pathology*; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis* / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D012867:Skin / Q000166:cytology / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D015342:DNA Probes; D018076:DNA, Complementary; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D011333:Pro-Opiomelanocortin