Dinparastisaleh Roshan, Mirsaeidi Mehdi
Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD 21218, USA.
Division of Pulmonary and Critical Care, University of Miami, Miami, FL 33146, USA.
Pharmaceuticals (Basel). 2021 Jan 8;14(1):45. doi: 10.3390/ph14010045.
The melanocortin system encompasses melanocortin peptides, five receptors, and two endogenous antagonists. Besides pigmentary effects generated by α-Melanocytic Hormone (α-MSH), new physiologic roles in sexual activity, exocrine secretion, energy homeostasis, as well as immunomodulatory actions, exerted by melanocortins, have been described recently. Among the most common and burdensome consequences of chronic inflammation is the development of fibrosis. Depending on the regenerative capacity of the affected tissue and the quality of the inflammatory response, the outcome is not always perfect, with the development of some fibrosis. Despite the heterogeneous etiology and clinical presentations, fibrosis in many pathological states follows the same path of activation or migration of fibroblasts, and the differentiation of fibroblasts to myofibroblasts, which produce collagen and α-SMA in fibrosing tissue. The melanocortin agonists might have favorable effects on the trajectories leading from tissue injury to inflammation, from inflammation to fibrosis, and from fibrosis to organ dysfunction. In this review we briefly summarized the data on structure, receptor signaling, and anti-inflammatory and anti-fibrotic properties of α-MSH and proposed that α-MSH analogues might be promising future therapeutic candidates for inflammatory and fibrotic diseases, regarding their favorable safety profile.
黑皮质素系统包括黑皮质素肽、五种受体和两种内源性拮抗剂。除了α-黑素细胞刺激素（α-MSH）产生的色素沉着作用外，最近还描述了黑皮质素在性活动、外分泌、能量稳态以及免疫调节作用方面的新生理作用。慢性炎症最常见且负担最重的后果之一是纤维化的发展。根据受影响组织的再生能力和炎症反应的质量，结果并不总是理想的，会出现一些纤维化。尽管病因和临床表现各不相同，但许多病理状态下的纤维化都遵循相同的成纤维细胞激活或迁移以及成纤维细胞向肌成纤维细胞分化的途径，肌成纤维细胞在纤维化组织中产生胶原蛋白和α-平滑肌肌动蛋白（α-SMA）。黑皮质素激动剂可能对从组织损伤到炎症、从炎症到纤维化以及从纤维化到器官功能障碍的过程产生有利影响。在本综述中，我们简要总结了关于α-MSH的结构、受体信号传导以及抗炎和抗纤维化特性的数据，并提出鉴于其良好的安全性，α-MSH类似物可能是未来治疗炎症性和纤维化疾病的有前景的候选药物。
