School of Basic Medical Science, Southwest Medical University, Luzhou 646000, China.
Department of Pathology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China.
Cells. 2022 Nov 26;11(23):3783. doi: 10.3390/cells11233783.
Liver fibrosis is a complicated process that involves different cell types and pathological factors. The excessive accumulation of extracellular matrix (ECM) and the formation of fibrotic scar disrupt the tissue homeostasis of the liver, eventually leading to cirrhosis and even liver failure. Myofibroblasts derived from hepatic stellate cells (HSCs) contribute to the development of liver fibrosis by producing ECM in the area of injuries. It has been reported that the secretion of the neuroendocrine hormone in chronic liver injury is different from a healthy liver. Activated HSCs and cholangiocytes express specific receptors in response to these neuropeptides released from the neuroendocrine system and other neuroendocrine cells. Neuroendocrine hormones and their receptors form a complicated network that regulates hepatic inflammation, which controls the progression of liver fibrosis. This review summarizes neuroendocrine regulation in liver fibrosis from three aspects. The first part describes the mechanisms of liver fibrosis. The second part presents the neuroendocrine sources and neuroendocrine compartments in the liver. The third section discusses the effects of various neuroendocrine factors, such as substance P (SP), melatonin, as well as α-calcitonin gene-related peptide (α-CGRP), on liver fibrosis and the potential therapeutic interventions for liver fibrosis.
肝纤维化是一个涉及多种细胞类型和病理因素的复杂过程。细胞外基质（ECM）的过度积累和纤维瘢痕的形成破坏了肝脏的组织稳态，最终导致肝硬化甚至肝功能衰竭。肝星状细胞（HSCs）来源的肌成纤维细胞通过在损伤部位产生 ECM 而促进肝纤维化的发展。据报道，慢性肝损伤时神经内分泌激素的分泌与健康肝脏不同。活化的 HSCs 和胆管细胞对神经内分泌系统和其他神经内分泌细胞释放的这些神经肽表达特定的受体。神经内分泌激素及其受体形成一个复杂的网络，调节肝脏炎症，从而控制肝纤维化的进展。本文从三个方面综述了神经内分泌在肝纤维化中的调节作用。第一部分描述了肝纤维化的机制。第二部分介绍了肝脏中的神经内分泌来源和神经内分泌区室。第三部分讨论了各种神经内分泌因子，如 P 物质（SP）、褪黑素以及α-降钙素基因相关肽（α-CGRP）对肝纤维化的影响，以及肝纤维化的潜在治疗干预措施。
