scholarly journals Activation of the Melanocortin-4 receptor signaling by α-MSH stimulates nerve-dependent mouse digit regeneration

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Hanqian Xu ◽  
Hailin Zhang ◽  
Yanqing Fang ◽  
Huiran Yang ◽  
Ying Chen ◽  
...  

Abstract Background Expression of Mc4r in peripheral organs indicates it has broader roles in organ homeostasis and regeneration. However, the expression and function of Mc4r in the mouse limb and digit has not been fully investigated. Our previous work showed that Mc4r−/− mice fail to regenerate the digit, but whether activation of MC4R signaling could rescue digit regeneration, or stimulate proximal digit regeneration is not clear. Results We analyzed the expression dynamics of Mc4r in the embryonic and postnatal mouse limb and digit using the Mc4r-gfp mice. We found that Mc4r-GFP is mainly expressed in the limb nerves, and in the limb muscles that are undergoing secondary myogenesis. Expression of Mc4r-GFP in the adult mouse digit is restricted to the nail matrix. We also examined the effect of α-MSH on mouse digit regeneration. We found that administration of α-MSH in the Mc4r+/− mice rescue the delayed regeneration of distal digit tip. α-MSH could rescue distal digit regeneration in denervated hindlimbs. In addition, α-MSH could stimulate regeneration of the proximally amputated digit, which is non-regenerative. Conclusions Mc4r expression in the mouse limb and digit is closely related to nerve tissues, and α-MSH/MC4R signaling has a neurotrophic role in mouse digit tip regeneration.

2010 ◽  
Vol 190 (4) ◽  
pp. i11-i11
Author(s):  
Hervé Falet ◽  
Alice Y. Pollitt ◽  
Antonija Jurak Begonja ◽  
Sarah E. Weber ◽  
Daniel Duerschmied ◽  
...  

2009 ◽  
Vol 297 (3) ◽  
pp. R803-R812 ◽  
Author(s):  
Jussara M. do Carmo ◽  
Lakshmi S. Tallam ◽  
John V. Roberts ◽  
Elizabeth L. Brandon ◽  
John Biglane ◽  
...  

The purpose of this study was to determine the long-term impact of obesity and related metabolic abnormalities in the absence and presence of hypertension on renal injury and salt-sensitivity of blood pressure. Markers of renal injury and blood pressure salt sensitivity were assessed in 52- to 55-wk-old normotensive melanocortin-4 receptor-deficient (MC4R−/−) mice and lean C57BL/6J wild-type (WT) mice and in 22-wk-old MC4R−/− and WT mice made hypertensive by NG-nitro-l-arginine methyl ester (l-NAME) in the drinking water for 8 wk. Old MC4R−/− mice were 60% heavier, hyperinsulinemic, and hyperleptinemic but had similar mean arterial pressure (MAP) as WT mice (115 ± 2 and 117 ± 2 mmHg) on normal salt diet (0.4% NaCl). A high-salt diet (4.0% NaCl) for 12 days did not raise MAP in obese or lean mice [ΔMAP: MC4R (−/−) 4 ± 2 mmHg; WT, 2 ± 1 mmHg]. Obese MC4R−/− mice had 23% greater glomerular tuft area and moderately increased GFR compared with WT mice. Bowman's space, total glomerular area, mesangial matrix, urinary albumin excretion (UAE), renal TGF-β and collagen expression were not significantly different between old MC4R−/− and WT mice. Renal lipid content was greater but renal macrophage count was markedly lower in MC4R−/− than WT mice. Mild increases in MAP during l-NAME treatment (∼16 mmHg) caused small, but greater, elevations in UAE, renal TGF-β content, and macrophage infiltration in MC4R−/− compared with WT mice without significant changes in glomerular structure. Thus despite long-term obesity and multiple metabolic abnormalities, MC4R−/− mice have no evidence of renal injury or salt-sensitivity of blood pressure. These observations suggest that elevations in blood pressure may be necessary for obesity and related metabolic abnormalities to cause major renal injury or that MC4R−/− mice are protected from renal injury by mechanisms that are still unclear.


2012 ◽  
Vol 106 (2) ◽  
pp. 201-210 ◽  
Author(s):  
Huxing Cui ◽  
Brittany L. Mason ◽  
Charlotte Lee ◽  
Akinori Nishi ◽  
Joel K. Elmquist ◽  
...  

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