Melanocortin 5 receptor signaling pathway in health and disease.
Melanocortin 5 receptor signaling pathway in health and disease.
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DOI：
10.1007/s00018-020-03511-0
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发表时间：
2020-10
期刊：
影响因子：
--
通讯作者：
Gong R
中科院分区：
文献类型：
--
作者：
Xu Y;Guan X;Zhou R;Gong R
黑皮质素激素系统通过其神经免疫内分泌活动在维持我们身体的稳态中起关键作用，并调节多种生理功能，包括黑素生成、炎症、免疫调节、肾上腺皮质类固醇生成、血液动力学、尿钠排泄、能量稳态、性功能和外分泌。所有黑皮质素的病理生物学作用均由黑皮质素受体传递。黑皮质素受体5（melanocortin receptor 5，MC5R）是最后一个被克隆和鉴定的黑皮质素受体，广泛表达于人类中枢神经系统和许多外周器官系统，但MC5R介导的黑皮质素能信号转导的确切作用尚不清楚。由于最近在开发MC5R的高选择性拟肽激动剂和拮抗剂方面的进展以及在MC5R敲除动物中的研究，我们对MC5R病理生物学的理解已经大大扩展和加强。有证据表明，MC5R在调节免疫反应和炎症反应中起关键作用，并且对于性行为、体温调节和外分泌分泌（如皮脂生成、泪腺分泌和性信息素的释放）的调节是关键的。因此，最近的转化努力集中在开发基于拮抗MC5R的用于皮脂溢和寻常痤疮的新型皮脂抑制疗法。相反，选择性MC5R激动剂已在免疫介导的疾病、代谢性内分泌病和其他疾病状况（如肾小球疾病和干眼、皮肤和口腔）中显示出有希望的有益效果。因此，MC5R介导的信号传导对健康至关重要。MC5R的治疗靶向代表了用于多种疾病的有前景和实用的治疗策略。这篇综述文章描述了MC5R介导的黑皮质激素系统的生物生理学，讨论了MC5R靶向治疗实验疾病模型的现有数据，并设想了治疗人类疾病的转化潜力。
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.
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影响因子：
3
作者：
Grieco, Paolo;Cai, Minying;Hruby, Victor J.
通讯作者：
Hruby, Victor J.
DOI：
10.1006/bbrc.1993.2125
发表时间：
1993-09-15
影响因子：
3.1
作者：
CHHAJLANI, V;MUCENIECE, R;WIKBERG, JES
通讯作者：
WIKBERG, JES
影响因子：
4.6
作者：
Eisinger, Magdalena;Li, Wen-Hwa;Seiberg, Miri
通讯作者：
Seiberg, Miri
影响因子：
9.8
作者：
Berg, Anna-Lena;Rafnsson, Arnar Thor;Arnadottir, Margret
通讯作者：
Arnadottir, Margret
DOI：
10.1006/bbrc.1994.1580
发表时间：
1994-05-16
影响因子：
3.1
作者：
GANTZ, I;SHIMOTO, Y;YAMADA, T
通讯作者：
YAMADA, T