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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Urologi och njurmedicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Urology and Nephrology (hsv//eng)

Nyckelord

Adrenocorticotropic Hormone

therapeutic use

Adult

Aged

Animals

Disease Models

Animal

Endothelial Cells

metabolism

Female

Glomerulonephritis

Membranous

complications

Hormones

therapeutic use

Humans

Male

Mesangial Cells

metabolism

Middle Aged

Podocytes

metabolism

Proteinuria

etiology

prevention & control

Rats

Receptor

Melanocortin

Type 1

agonists

biosynthesis

Urothelium

cytology

metabolism

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)