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Dermal Melanocortin Receptor Rebound in Diffuse Systemic Sclerosis after Anti-TGFβ1 Antibody Therapy
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. (farmaceutisk bioinformatik)
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2012 (English)In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 76, no 5, 478-482 p.Article in journal (Refereed) Published
Abstract [en]

Disturbed transforming growth factor beta (TGFβ) signalling leads to enhanced synthesis of extracellular matrix (ECM), which is manifested as systemic sclerosis (SSc), but this may be attenuated by the melanocortin system. Here, we report of rebound reaction in the gene expression of melanocortin receptor (MCR) subtypes and of the precursor of these receptors' ligands, the pro-opio-melanocortin protein (POMC), in the acute skin lesion of diffuse systemic sclerosis (dSSc) after treatment with a recombinant human anti-TGFβ1 antibody. Biopsies, taken from the leading edge of the skin lesion, before and after treatment of a patient with recent onset dSSc, were examined. Before treatment, increased levels of TGFβ mRNA and suppressed levels of POMC mRNA and MCR subtypes MC 1-3, 5R mRNAs were seen in the lesion, compared with healthy controls. After treatment, there was a rebound expression of POMC, MC 2, 3, 5R mRNAs. As the melanocortin system regulates collagen and melanin production, our findings add a new understanding to the pathogenetic mechanisms involved in the acute skin lesion of dSSc, which is characterized by enhanced ECM formation and changes in skin pigmentation.

Place, publisher, year, edition, pages
2012. Vol. 76, no 5, 478-482 p.
Keyword [en]
collagen, melanin, melanocortin receptor, messenger RNA, proopiomelanocortin, protein precursor, transforming growth factor beta1, article, controlled study, extracellular matrix, gene expression, human, human cell, priority journal, punch biopsy, skin biopsy, skin defect, skin pigmentation, skinfold thickness, systemic sclerosis
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-184948DOI: 10.1111/j.1365-3083.2012.02757.xISI: 000309745900005OAI: oai:DiVA.org:uu-184948DiVA: diva2:570361
Available from: 2012-11-19 Created: 2012-11-15 Last updated: 2012-11-21Bibliographically approved

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Wikberg, Jarl E. S.
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