Current Perspectives of Neuroendocrine Regulation in Liver Fibrosis

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.