| First Author | Böhm M | Year | 2004 |
| Journal | J Biol Chem | Volume | 279 |
| Issue | 8 | Pages | 6959-66 |
| PubMed ID | 14645373 | Mgi Jnum | J:88960 |
| Mgi Id | MGI:3037510 | Doi | 10.1074/jbc.M312549200 |
| Citation | Bohm M, et al. (2004) Collagen metabolism is a novel target of the neuropeptide alpha-melanocyte-stimulating hormone. J Biol Chem 279(8):6959-66 |
| abstractText | Suppression of collagen synthesis is a major therapeutic goal in the treatment of fibrotic disorders. We show here that alpha-melanocyte-stimulating hormone (alpha-MSH), a neuropeptide well known for its pigment-inducing capacity, modulates collagen synthesis and deposition. Alpha-MSH in vitro suppresses the synthesis of collagen types I, III, and V and down-regulates the secretion of procollagen type I C-terminal peptide (PICP) in human dermal fibroblasts treated with the fibrogenic cytokine transforming growth factor-beta1 (TGF-beta1). Alpha-MSH did not interfere with TGF-beta1 signaling, because TGF-beta1-induced expression of collagen mRNA was not affected, implying a posttranscriptional mechanism. Human dermal fibroblasts in vitro express a high affinity binding site for MSH, which was identified by reverse transcription PCR and immunofluorescence analysis as the melanocortin-1 receptor (MC-1R). Immunohistochemical studies on normal adult human skin confirmed MC-1R expression in distinct dermal fibroblastic cells. The MC-1R on fibroblasts appears to be functionally relevant because alpha-MSH increased the amount of intracellular cAMP, and coincubation with a synthetic peptide corresponding to the human Agouti signaling protein abrogated the inhibition of TGF-beta1-induced PICP secretion by alpha-MSH. To assess the in vivo relevance of these findings, a mouse model was used in which dermal fibrosis was induced by repetitive intracutaneous injections with TGF-beta1. The inductive activity of TGF-beta1 on collagen deposition and the number of dermal cells immunoreactive for vimentin and alpha-smooth muscle actin was significantly suppressed by injection of alpha-MSH. Melanocortins such as alpha-MSH may therefore represent a novel class of modulators with potential usefulness for the treatment of fibrotic disorders. |
