Effects of melanocortin 1 receptor agonists in experimental nephropathies.

Annika Lindskog Jonsson, Anna Granqvist, Johannes Elvin, Martin Johansson, Börje Haraldsson, Jenny Nyström

Research output: Contribution to journalArticlepeer-review

15 Citations (SciVal)
137 Downloads (Pure)

Abstract

Nephrotic syndrome, characterized by massive proteinuria, is caused by a large group of diseases including membranous nephropathy (MN) and focal segmental glomerulosclerosis (FSGS). Although the underlying mechanisms are beginning to unravel, therapy is unspecific and far from efficient. It has been suggested that adrenocorticotropic hormone (ACTH) has beneficial effects in patients with MN and possibly in other nephrotic diseases. We have previously reported that ACTH may act directly on podocytes through the melanocortin 1 receptor (MC1R). In the present study, we evaluate the effect of highly specific MC1R agonists in two different nephrotic disease models. Experimental MN: Passive Heymann nephritis (PHN) was induced in rats that were treated for four weeks with MS05, a selective MC1R agonist, or saline. The degree of albuminuria was significantly reduced over time and the effect was sustained one week after treatment withdrawal (p<0.05). Experimental FSGS: Based on a dose-response study, two doses of adriamycin were used for induction of nephropathy in Balb/c mice. Mice were treated with either a synthetic MC1R agonist (BMS-470539), with α-melanocyte stimulating hormone (α-MSH) or with saline. There was no beneficial effect of treatment. In summary, MC1R agonists reduce albuminuria and improve morphology in experimentally induced MN whereas they have no effect in experimental FSGS. The results illustrate the differences in these podocytopathies in terms of signaling mechanisms underlying proteinuria, and progression of disease.
Original languageEnglish
Article numbere87816
JournalPLoS ONE
Volume9
Issue number1
DOIs
Publication statusPublished - 2014

Subject classification (UKÄ)

  • Cancer and Oncology
  • Cell and Molecular Biology

Fingerprint

Dive into the research topics of 'Effects of melanocortin 1 receptor agonists in experimental nephropathies.'. Together they form a unique fingerprint.

Cite this