Metabolic Adaptation of Activated Hepatic Stellate Cells During Hepatic Fibrogenesis

HF (hepatic fibrosis) is a common wound-repair reaction in injured liver induced by a variety of pathogenic factors. The most distinct and crucial step during HF is the activation of HSCs (hepatic stellate cells). Once activated, HSC transdifferentiate into MFB (myofibroblasts) and acquire the abilities to be chemotactic, proliferate, secrete profibrogenic factors and ECM (extracellular matrix) components including fibrillar collagens type I and III. The excessive accumulation of ECM disrupts the physiological structure of liver and ultimately leads to liver dysfunction and portal hypertension. A series of metabolic alterations occur during the activation of HSCs including upregulation of both glycolysis and oxidative phosphorylation, elevation of glutaminolysis, and autophagic degradation of retinyl ester lipid stored in the cell cytoplasm. These metabolic reprogramming processes generate sufficient substances and energy required for HSCs activation and positively regulate fibrogenic signaling pathways. By elucidating these metabolic alterations and relative mechanisms, novel therapeutic targets and drugs are being discovered against HF.

CSTR: 32200.14.cjcb.2021.10.0014