The clinical effectiveness of adrenocorticotropin in inducing remission of steroid-resistant nephrotic syndrome points to a steroidogenic-independent anti-proteinuric activity of melanocortins. However, which melanocortin receptors (MCR) convey this beneficial effect and if systemic or podocyte-specific mechanisms are involved remain uncertain. In vivo, wild-type (WT) mice developed heavy proteinuria and kidney dysfunction following Adriamycin insult, concomitant with focal segmental glomerulosclerosis (FSGS) and podocytopathy, marked by loss of podocin and synaptopodin, podocytopenia and extensive foot process effacement on electron microscopy. All these pathologic findings were prominently attenuated by NDP-MSH, a potent non-steroidogenic pan-MCR agonist. Surprisingly, MC1R deficiency in MC1R-null mice barely affected the severity of Adriamycin-elicited injury. Moreover, the beneficial effect of NDP-MSH was completely preserved in MC1R-null mice, suggesting that MC1R is likely non-essential for the protective action. A direct podocyte effect seems to contribute to the beneficial effect of NDP-MSH, because Adriamycin-inflicted cytopathic signs in primary podocytes prepared from WT mice were all mitigated by NDP-MSH, including apoptosis, loss of podocyte markers, de novo expression of the podocyte injury marker desmin, actin cytoskeleton derangement and podocyte hypermotility. Consistent with in vivo findings, the podoprotective activity of NDP-MSH was fully preserved in MC1R-null podocytes. Mechanistically, MC1R expression was predominantly distributed to glomerular endothelial cells in glomeruli but negligibly noted in podocytes in vivo and in vitro, suggesting that MC1R signaling is unlikely involved in direct podocyte protection. Ergo, melanocortin therapy protects against podocyte injury and ameliorates proteinuria and glomerulopathy in experimental FSGS, at least in part, via a podocyte-specific non-MC1R-mediated melanocortinergic signaling.
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http://dx.doi.org/10.1042/CS20200016 | DOI Listing |
BMJ Open
December 2024
Clinical Medicine, School of Medicine and Population Health, The University of Sheffield, Sheffield, UK
Introduction: Cortisol is an essential stress hormone and failure of its production, known as adrenal insufficiency (AI), is associated with significant mortality due to adrenal crisis. The Short Synacthen Test (SST) is the current diagnostic test of choice for AI, but it is both invasive and resource intensive. Globally, there is an unmet need for a non-invasive, cost-effective test.
View Article and Find Full Text PDFZhong Nan Da Xue Xue Bao Yi Xue Ban
July 2024
Department of Endocrinology &Metabolism, West China Hospital, Sichuan University, Chengdu 610041.
Cushing's disease is a rare endocrine disorder characterized by hypercortisolism. Chronic elevated cortisol levels can lead to dysfunction or complications in multiple organs of systems, including cardiovascular, glucose, and bone metabolism, severely impacting patients' quality of life and posing life-threatening risks. Surgery is the first-line treatment for Cushing's disease.
View Article and Find Full Text PDFPharmacol Res Perspect
February 2025
Department of Cardiology and Pneumology, University of Göttingen Medical Center, Göttingen, Germany.
Cachexia is a multifactorial metabolic syndrome characterized by weight and skeletal muscle loss caused by underlying illnesses such as cancer, heart failure, and renal failure. Inflammation, insulin resistance, increased muscle protein degradation, decreased food intake, and anorexia are the primary pathophysiological drivers of cachexia. Cachexia causes physical deterioration and functional impairment, loss of quality of life, lower response to active treatment, and ultimately morbidity and mortality, while the difficulties in tackling cachexia in its advanced phases and the heterogeneity of the syndrome among patients require an individualized and multidisciplinary approach from an early stage.
View Article and Find Full Text PDFJ Am Anim Hosp Assoc
January 2025
From the Washington State University College of Veterinary Medicine, Pullman, Washington.
A 7 wk old female spayed domestic shorthair was evaluated for 3 days of lethargy and anorexia 1 wk after ovariohysterectomy. On presentation, she was weak, dehydrated, and hypotensive. Blood work showed azotemia, hyponatremia, hyperkalemia, hyperphosphatemia, and hyperproteinemia.
View Article and Find Full Text PDFMar Drugs
November 2024
Research Institute of Basic Sciences, Incheon National University, Incheon 22012, Republic of Korea.
, a salt-tolerant plant, has demonstrated antioxidant effects, the ability to prevent prostate enlargement, antifungal properties, and skin moisturizing benefits. This study aimed to explore the anti-melanogenic potential of the 70% ethanol extract of (TME) along with its ethyl acetate (TME-EA) and water (TME-A) fractions. TME (10-200 µg/mL), TME-EA (1-15 µg/mL), and TME-A (100-1000 µg/mL) were prepared and applied to B16F10 cells with or without α-MSH for 72 h.
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