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Melanocortin 1 Receptor Agonists Reduce Proteinuria

Lindskog, Annika; Ebefors, Kerstin; Johansson, Martin LU ; Stefansson, Bergur; Granqvist, Anna; Arnadottir, Margret; Berg, Anna-Lena LU ; Nystrom, Jenny and Haraldsson, Borje (2010) In Journal of the American Society of Nephrology 21(8). p.1290-1298
Abstract
Membranous nephropathy is one of the most common causes of nephrotic syndrome in adults. Recent reports suggest that treatment with adrenocorticotropic hormone (ACTH) reduces proteinuria, but the mechanism of action is unknown Here, we identified gene expression of the melanocortin receptor MC1R in podocytes, glomerular endothelial cells, mesangial cells, and tubular epithelial cells. Podocytes expressed most MC1R protein, which colocalized with synaptopodin but not with an endothelial-specific lectin. We treated rats with passive Heymann nephritis (PHN) with MS05, a specific MC1R agonist, which significantly reduced proteinuria compared with untreated PHN rats (P < 0.01). Furthermore, treatment with MC1R agonists improved podocyte... (More)
Membranous nephropathy is one of the most common causes of nephrotic syndrome in adults. Recent reports suggest that treatment with adrenocorticotropic hormone (ACTH) reduces proteinuria, but the mechanism of action is unknown Here, we identified gene expression of the melanocortin receptor MC1R in podocytes, glomerular endothelial cells, mesangial cells, and tubular epithelial cells. Podocytes expressed most MC1R protein, which colocalized with synaptopodin but not with an endothelial-specific lectin. We treated rats with passive Heymann nephritis (PHN) with MS05, a specific MC1R agonist, which significantly reduced proteinuria compared with untreated PHN rats (P < 0.01). Furthermore, treatment with MC1R agonists improved podocyte morphology and reduced oxidative stress. In summary, podocytes express MC1R, and MC1R agonism reduces proteinuria, improves glomerular morphology, and reduces oxidative stress in nephrotic rats with PHN. These data may explain the proteinuria-reducing effects of ACTH observed in patients with membranous nephropathy, and MC1R agonists may provide a new therapeutic option for these patients. (Less)
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type
Contribution to journal
publication status
published
subject
in
Journal of the American Society of Nephrology
volume
21
issue
8
pages
1290 - 1298
publisher
American Society of Nephrology
external identifiers
  • wos:000280746200014
  • scopus:77955609123
ISSN
1046-6673
DOI
10.1681/ASN.2009101025
language
English
LU publication?
yes
id
e3a62ece-16a8-48b8-8246-db266613c597 (old id 1675422)
date added to LUP
2010-09-22 09:55:02
date last changed
2018-07-15 03:54:11
@article{e3a62ece-16a8-48b8-8246-db266613c597,
  abstract     = {Membranous nephropathy is one of the most common causes of nephrotic syndrome in adults. Recent reports suggest that treatment with adrenocorticotropic hormone (ACTH) reduces proteinuria, but the mechanism of action is unknown Here, we identified gene expression of the melanocortin receptor MC1R in podocytes, glomerular endothelial cells, mesangial cells, and tubular epithelial cells. Podocytes expressed most MC1R protein, which colocalized with synaptopodin but not with an endothelial-specific lectin. We treated rats with passive Heymann nephritis (PHN) with MS05, a specific MC1R agonist, which significantly reduced proteinuria compared with untreated PHN rats (P &lt; 0.01). Furthermore, treatment with MC1R agonists improved podocyte morphology and reduced oxidative stress. In summary, podocytes express MC1R, and MC1R agonism reduces proteinuria, improves glomerular morphology, and reduces oxidative stress in nephrotic rats with PHN. These data may explain the proteinuria-reducing effects of ACTH observed in patients with membranous nephropathy, and MC1R agonists may provide a new therapeutic option for these patients.},
  author       = {Lindskog, Annika and Ebefors, Kerstin and Johansson, Martin and Stefansson, Bergur and Granqvist, Anna and Arnadottir, Margret and Berg, Anna-Lena and Nystrom, Jenny and Haraldsson, Borje},
  issn         = {1046-6673},
  language     = {eng},
  number       = {8},
  pages        = {1290--1298},
  publisher    = {American Society of Nephrology},
  series       = {Journal of the American Society of Nephrology},
  title        = {Melanocortin 1 Receptor Agonists Reduce Proteinuria},
  url          = {http://dx.doi.org/10.1681/ASN.2009101025},
  volume       = {21},
  year         = {2010},
}