Published online Jun 14, 2023. doi: 10.3748/wjg.v29.i22.3422
Peer-review started: February 15, 2023
First decision: March 28, 2023
Revised: April 10, 2023
Accepted: May 11, 2023
Article in press: May 11, 2023
Published online: June 14, 2023
Hepatic fibrosis is a common pathological process of chronic liver diseases with various causes, which can progress to cirrhosis.
To evaluate the effect and mechanism of action annexin (Anx)A1 in liver fibrosis and how this could be targeted therapeutically.
CCl4 (20%) and active N-terminal peptide of AnxA1 (Ac2-26) and N-formylpep
Compared with the control group, AnxA1, transforming growth factor (TGF)-β1, interleukin (IL)-1β and IL-6 expression in the liver of mice with hepatic fibrosis induced by CCl4 was significantly increased, which promoted collagen deposition and expression of α-smooth muscle actin (α-SMA), collagen type I and connective tissue growth factor (CTGF), and increased progressively with time. CCl4 induced an increase in TGF-β1, IL-1β and IL-6 in liver tissue of AnxA1 knockout mice, and the degree of liver inflammation and fibrosis and expression of α-SMA, collagen I and CTGF were significantly increased compared with in wild-type mice. After treatment with Ac2-26, expression of liver inflammatory factors, degree of collagen deposition and expression of a-SMA, collagen I and CTGF were decrea
AnxA1 inhibited liver fibrosis in mice, and its mechanism may be related to inhibition of HSC Wnt/β-catenin pathway activation by targeting formylpeptide receptors to regulate macrophage function.
Core Tip: Hepatic stellate cells (HSCs) are the main receiver of inflammatory signals and the main promoter of fibrosis. Kupffer cells are activated by damage-associated molecular patterns or lipopolysaccharide, and other pathogen-associated molecular patterns, producing and releasing cytokines to activate HSCs, causing secretion and deposition of extracellular matrix and liver fibrosis. Annexin (Anx)A1 is a glucocorticoid regulatory protein that enhances efferocytosis in macrophages, inhibits activation of phospholipase A2, downregulates expression of inflammatory arachidonic acid, and negatively regulates inflammatory cells and factors. Whether AnxA1 is involved in the formation of liver fibrosis and its mechanism of action were the focus of this study.