Change of Melanocortin Receptor Expression in Rat Kidney Ischemia–Reperfusion Injury

Lee, Y.S.; Park, J.J.; Chung, Ku Yong

doi:10.1016/j.transproceed.2008.07.101

Cited by 16 publications

(16 citation statements)

References 6 publications

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“…However, which type of MCR is expressed in the kidney and in glomeruli remains highly controversial. For instance, MC3R, MC4R and MC5R were found in both cortex and medulla of murine kidneys32; whereas, Lee et al 33. only demonstrated MC1R and MC3R expression in rat kidney.…”

Section: Discussionmentioning

confidence: 96%

MC1R is dispensable for the proteinuria reducing and glomerular protective effect of melanocortin therapy

Qiao

Berg

Wang

et al. 2016

Sci Rep

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Melanocortin therapy by using adrenocorticotropic hormone (ACTH) or non-steroidogenic melanocortin peptides attenuates proteinuria and glomerular injury in experimental glomerular diseases and induces remission of nephrotic syndrome in patients with diverse glomerulopathies, even those resistant to steroids. The underlying mechanism remains elusive, but the role of melanocortin 1 receptor (MC1R) has been implicated and was examined here. Four patients with congenital red hair color and nephrotic syndrome caused by idiopathic membranous nephropathy or focal segmental glomerulosclerosis were confirmed by gene sequencing to bear dominant-negative MC1R mutations. Despite prior corticosteroid resistance, all patients responded to ACTH monotherapy and ultimately achieved clinical remission, inferring a steroidogenic-independent and MC1R-dispensable anti-proteinuric effect of melanocortin signaling. In confirmatory animal studies, the protective effect of [Nle4, D-Phe7]-α-melanocyte stimulating hormone (NDP-MSH), a potent non-steroidogenic pan-melanocortin receptor agonist, on the lipopolysaccharide elicited podocytopathy was completely preserved in MC1R-null mice, marked by reduced albuminuria and diminished histologic signs of podocyte injury. Moreover, in complementary in vitro studies, NDP-MSH attenuated the lipopolysaccharide elicited apoptosis, hypermotility and impairment of filtration barrier function equally in primary podocytes derived from MC1R-null and wild-type mice. Collectively, our findings suggest that melanocortin therapy confers a proteinuria reducing and podoprotective effect in proteinuric glomerulopathies via MC1R-independent mechanisms.

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Section: Discussionmentioning

confidence: 96%

MC1R is dispensable for the proteinuria reducing and glomerular protective effect of melanocortin therapy

Qiao

Berg

Wang

et al. 2016

Sci Rep

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“…α‐Melanocyte‐stimulating hormone (α‐MSH) is an endogenous hormone that inhibits inflammatory, cytotoxic, and apoptotic pathways, thus preventing renal injury caused by I/R‐induced AKI 9, 10, 11. Additionally, α‐MSH has direct protective effects on the kidney, which may result from stimulation of the melanocortin receptors (MCRs) 1 and 3 in the outer renal medulla 12. The apical membrane of collecting ducts, including the principal cells in the cortical collecting duct, also express MCR1 and may play a protective role in I/R injury 11…”

Section: Introductionmentioning

confidence: 99%

ABT‐719 for the Prevention of Acute Kidney Injury in Patients Undergoing High‐Risk Cardiac Surgery: A Randomized Phase 2b Clinical Trial

McCullough

Bennett‐Guerrero

Chawla³

et al. 2016

JAHA

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BackgroundPatients undergoing cardiac surgeries with cardiopulmonary bypass (on‐pump) have a high risk for acute kidney injury (AKI). We tested ABT‐719, a novel α‐melanocyte‐stimulating hormone analog, for prevention of AKI in postoperative cardiac surgery patients.Methods and ResultsThis phase 2b randomized, double‐blind, placebo‐controlled trial included adult patients with stable renal function undergoing high‐risk on‐pump cardiac surgery in the United States and Denmark. Participants received placebo (n=61) or cumulative ABT‐719 doses of 800 (n=59), 1600 (n=61), or 2100 μg/kg (n=59). Primary outcome was development of AKI based on Acute Kidney Injury Network (AKIN) criteria, measured utilizing preoperative creatinine value and maximum value within 48 hours and urine output within the first 42 hours postsurgery. Secondary outcomes included incidence of AKI based on maximal changes from baseline in novel AKI biomarkers over a 72‐hour period after clamp release and length of intensive care unit stays through 90 days postsurgery. A total of 65.5%, 62.7%, and 69.6% of patients in the 800‐, 1600‐, and 2100‐μg/kg groups, respectively, developed AKI (stages 1, 2, and 3 combined) versus 65.5% in the placebo group (for each pair‐wise comparison with placebo, P=0.966, 0.815, and 0.605, respectively). Adverse events occurred at a similar rate in all treatment groups.Conclusions ABT‐719 treatment did not lower AKI incidence using AKIN criteria, influence the elevations of novel biomarkers, or change 90‐day outcomes in patients after cardiac surgery.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique Identifier: NCT01777165.

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“…The anti-inflammatory capacities of α-MSH are based on modulation of antigen presenting cells and reduced production of cytokines such as IL-1β, TNF-α and IL-6 [28], [30], [31]. Although MCR1 and MCR3 expression in the kidney is slightly decreased after renal I/R, renal expression of these receptors suggests α-MSH treatment might be locally protective [28], [32]. Chiao et al showed using isolated perfused kidneys after renal ischemia that addition of α-MSH to the perfusion solution improves renal function indicating that α-MSH mediated renoprotection is based on a renal binding to MCR's [13].…”

Section: Discussionmentioning

confidence: 99%

α-Melanocyte Stimulating Hormone Treatment in Pigs Does Not Improve Early Graft Function in Kidney Transplants from Brain Dead Donors

et al. 2014

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Delayed graft function and primary non-function are serious complications following transplantation of kidneys derived from deceased brain dead (DBD) donors. α-melanocyte stimulating hormone (α-MSH) is a pleiotropic neuropeptide and its renoprotective effects have been demonstrated in models of acute kidney injury. We hypothesized that α-MSH treatment of the recipient improves early graft function and reduces inflammation following DBD kidney transplantation. Eight Danish landrace pigs served as DBD donors. After four hours of brain death both kidneys were removed and stored for 18 hours at 4°C in Custodiol preservation solution. Sixteen recipients were randomized in a paired design into two treatment groups, transplanted simultaneously. α-MSH or a vehicle was administered at start of surgery, during reperfusion and two hours post-reperfusion. The recipients were observed for ten hours following reperfusion. Blood, urine and kidney tissue samples were collected during and at the end of follow-up. α-MSH treatment reduced urine flow and impaired recovery of glomerular filtration rate (GFR) compared to controls. After each dose of α-MSH, a trend towards reduced mean arterial blood pressure and increased heart rate was observed. α-MSH did not affect expression of inflammatory markers. Surprisingly, α-MSH impaired recovery of renal function in the first ten hours following DBD kidney transplantation possibly due to hemodynamic changes. Thus, in a porcine experimental model α-MSH did not reduce renal inflammation and did not improve short-term graft function following DBD kidney transplantation.

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Change of Melanocortin Receptor Expression in Rat Kidney Ischemia–Reperfusion Injury

Cited by 16 publications

References 6 publications

MC1R is dispensable for the proteinuria reducing and glomerular protective effect of melanocortin therapy

MC1R is dispensable for the proteinuria reducing and glomerular protective effect of melanocortin therapy

ABT‐719 for the Prevention of Acute Kidney Injury in Patients Undergoing High‐Risk Cardiac Surgery: A Randomized Phase 2b Clinical Trial

α-Melanocyte Stimulating Hormone Treatment in Pigs Does Not Improve Early Graft Function in Kidney Transplants from Brain Dead Donors

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