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|Title:||Collagen Metabolism Is a Novel Target of the Neuropeptide α-Melanocyte-stimulating Hormone||Authors:||Böhm, M.
|Issue Date:||20-Feb-2004||Citation:||Böhm, M., Raghunath, M., Sunderkötter, C., Schiller, M., Ständer, S., Brzoska, T., Cauvet, T., Schiöth, H.B., Schwarz, T., Luger, T.A. (2004-02-20). Collagen Metabolism Is a Novel Target of the Neuropeptide α-Melanocyte-stimulating Hormone. Journal of Biological Chemistry 279 (8) : 6959-6966. ScholarBank@NUS Repository. https://doi.org/10.1074/jbc.M312549200||Abstract:||Suppression of collagen synthesis is a major therapeutic goal in the treatment of fibrotic disorders. We show here that α -melanocyte-stimulating hormone (α-MSH), a neuropeptide well known for its pigment-inducing capacity, modulates collagen synthesis and deposition. α-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-β1 (TGF-β1). α-MSH did not interfere with TGF-β1 signaling, because TGF-β 1-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 α-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-β 1-induced PICP secretion by α-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-β 1. The inductive activity of TGF-β1 on collagen deposition and the number of dermal cells immunoreactive for vimentin and α-smooth muscle actin was significantly suppressed by injection of α-MSH. Melanocortins such as α-MSH may therefore represent a novel class of modulators with potential usefulness for the treatment of fibrotic disorders.||Source Title:||Journal of Biological Chemistry||URI:||http://scholarbank.nus.edu.sg/handle/10635/87732||ISSN:||00219258||DOI:||10.1074/jbc.M312549200|
|Appears in Collections:||Staff Publications|
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