Current Perspectives of Neuroendocrine Regulation in Liver Fibrosis

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.

Keywords: hepatic stellate cells; liver fibrosis; neuroendocrine hormones; neuroendocrine regulation; tissue homeostasis.

Publication types

  • Review

MeSH terms

  • Hepatic Stellate Cells* / metabolism
  • Humans
  • Liver Cirrhosis* / metabolism
  • Myofibroblasts / metabolism
  • Neurosecretory Systems / metabolism

Grant support

This research was funded by the National Natural Science Foundation of China (No. 81873563) to Y.W., funding from Southwest Medical University (2021ZKQN018) to B.Z., and the VA Merit awards to Meng (1I01BX001724) from the United States Department of Veteran’s Affairs Biomedical Laboratory Research and Development Service, The project described was supported by the Indiana University Health—Indiana University School of Medicine Strategic Research Initiative. Meng acknowledges the support from PSC Partners Seeking a Cure. This material is the result of work supported by resources at Richard L. Roudebush VA Medical Center, Indianapolis, IN, USA. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. And The APC was funded by the National Natural Science Foundation of China (No. 81873563).