Please use this identifier to cite or link to this item:
|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|
Show full item record
Files in This Item:
There are no files associated with this item.
checked on Aug 12, 2020
WEB OF SCIENCETM
checked on Aug 12, 2020
checked on Aug 2, 2020
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.