Melanocortin 1 receptor agonists reduce proteinuria.
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.
Lindskog
Annika
A
Department of Molecular and Clinical Nephrology, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. annika.lindskog@wlab.gu.se
Ebefors
Kerstin
K
Johansson
Martin E
ME
Stefánsson
Bergur
B
Granqvist
Anna
A
Arnadottir
Margret
M
Berg
Anna-Lena
AL
Nyström
Jenny
J
Haraldsson
Börje
B
D000324:Adrenocorticotropic Hormone / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000818:Animals; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000150:complications; D006728:Hormones / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D050527:Mesangial Cells / Q000378:metabolism; D008875:Middle Aged; D050199:Podocytes / Q000378:metabolism; D011507:Proteinuria / Q000209:etiology / Q000517:prevention & control*; D051381:Rats; D044102:Receptor, Melanocortin, Type 1 / Q000819:agonists* / Q000096:biosynthesis; D019459:Urothelium / Q000166:cytology / Q000378:metabolism
D006728:Hormones; D044102:Receptor, Melanocortin, Type 1; D000324:Adrenocorticotropic Hormone