Melanocortin 5 receptor signaling pathway in health and disease
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Cellular and Molecular Life Sciences
UNSOLICITED REVIEW
Melanocortin 5 receptor signaling pathway in health and disease Yahong Xu1,2 · Xuejing Guan3 · Rong Zhou2 · Rujun Gong1,3 Received: 22 January 2020 / Revised: 17 March 2020 / Accepted: 24 March 2020 © Springer Nature Switzerland AG 2020
Abstract Melanocortin hormone system plays a key role in maintaining the homeostasis of our body via their neuro-immune-endocrine activities and regulates a diverse array of physiological functions, including melanogenesis, inflammation, immunomodulation, adrenocortical steroidogenesis, hemodynamics, natriuresis, energy homeostasis, sexual function, and exocrine secretion. The pathobiologic actions of all melanocortins are conveyed by melanocortin receptors. As the last melanocortin receptor to be cloned and characterized, melanocortin receptor 5 (MC5R) is widely expressed in both central nervous system and a number of peripheral organ systems in man. However, the exact effect of the MC5R mediated melanocortinergic signaling remains largely uncertain. Owing to the recent advances in developing highly selective peptidomimetic agonists and antagonists of MC5R and also to studies in MC5R knockout animals, our understanding of MC5R pathobiology has been greatly expanded and strengthened. Evidence suggests that MC5R plays a key role in governing immune reaction and inflammatory response, and is pivotal for the regulation of sexual behavior, thermoregulation, and exocrine secretion, like sebogenesis, lacrimal secretion and release of sex pheromones. As such, recent translational efforts have focused on developing novel sebum-suppressive therapies for seborrhoea and acne vulgaris based on antagonizing MC5R. Conversely, selective MC5R agonists have demonstrated promising beneficial effects in immune-mediated diseases, metabolic endocrinopathies and other disease conditions, such as glomerular diseases and dry eyes, skin and mouth. Thus, MC5R-mediated signaling is essential for health. Therapeutic targeting of MC5R represents a promising and pragmatic therapeutic strategy for diverse diseases. This review article delineates the biophysiology of MC5R-mediated biophysiology of the melanocortin hormone system, discusses the existing data on MC5R-targeted therapy in experimental disease models, and envisages the translational potential for treating human diseases. Keywords Melanocortin · Melanocortin receptor · Sebogenesis · Kidney · Muscle · Autoimmune uveitis · Immune response
Introduction The melanocortins are a family of neuropeptide hormones. As a key part of the neuroimmunoendocrine axis, the melanocortin system plays a pivotal role in a number of Yahong Xu and Xuejing Guan are co-first authors that contributed equally to this work. * Rujun Gong [email protected] 1
Division of Kidney Disease and Hypertension, Department of Medicine, Brown University School of Medicine, Providence, RI, USA
2
Department of Nephrology, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China
3
Division of Nephrology, D
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