Melanocortin System in Kidney Homeostasis and Disease: Novel Therapeutic Opportunities.

Mingyang Chang,Bohan Chen,Rujun Gong,Lance D Dworkin,James Shaffner

doi:10.3389/fphys.2021.651236

Mingyang Chang, Bohan Chen + Show 3 more

Open Access

https://doi.org/10.3389/fphys.2021.651236

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Journal: Frontiers in physiology	Publication Date: Feb 24, 2021
Citations: 9	License type: CC BY 4.0

Affiliation: University of Toledo

Abstract

Melanocortin peptides, melanocortin receptors, melanocortin receptor accessory proteins, and endogenous antagonists of melanocortin receptors are the key components constituting the melanocortin hormone system, one of the most complex and important hormonal systems in our body. A plethora of evidence suggests that melanocortins possess a protective activity in a variety of kidney diseases in both rodent models and human patients. In particular, the steroidogenic melanocortin peptide adrenocorticotropic hormone (ACTH), has been shown to exert a beneficial effect in a number of kidney diseases, possibly via a mechanism independent of its steroidogenic activity. In patients with steroid-resistant nephrotic glomerulopathy, ACTH monotherapy is still effective in inducing proteinuria remission. This has inspired research on potential implications of the melanocortin system in glomerular diseases. However, our understanding of the role of the melanocortinergic pathway in kidney disease is very limited, and there are still huge unknowns to be explored. The most controversial among these is the identification of effector cells in the kidney as well as the melanocortin receptors responsible for conveying the renoprotective action. This review article introduces the melanocortin hormone system, summarizes the existing evidence for the expression of melanocortin receptors in the kidney, and evaluates the potential strategy of melanocortin therapy for kidney disease.

Highlights

The melanocortin system is a neuroimmune endocrine hormone system that encompasses five melanocortin receptors (MC1R∼MC5R), four pro-opiomelanocortin (POMC)-derived melanocortin peptides (ACTH, α-MSH, β-MSH, and γ-MSH) (Figure 1), endogenous antagonists, i.e., agouti-signaling protein (ASP or ASIP) and agouti-related protein (AGRP), and melanocortin receptor accessory proteins (MRAP) (Table 1) (Gantz and Fong, 2003)
A growing body of evidence recently suggests that adrenocorticotropic hormone (ACTH) monotherapy is able to effectively alleviate steroidresistant nephrotic syndrome, denoting that ACTH achieves its renal protection via mechanisms beyond adrenocortical steroidogenesis (Gong, 2011)
Given that multiple kidney cells express MCRs, it is posited that the kidney may be a quintessential effector organ of the melanocortin hormone system and that melanocortin peptides may directly target diverse types of kidney cells to convey a renoprotective activity

Summary

Introduction

The melanocortin system is a neuroimmune endocrine hormone system that encompasses five melanocortin receptors (MC1R∼MC5R), four pro-opiomelanocortin (POMC)-derived melanocortin peptides (ACTH, α-MSH, β-MSH, and γ-MSH) (Figure 1), endogenous antagonists, i.e., agouti-signaling protein (ASP or ASIP) and agouti-related protein (AGRP), and melanocortin receptor accessory proteins (MRAP) (Table 1) (Gantz and Fong, 2003).

Results

Conclusion