Autocrine Netrin-1 Signaling in Hepatic Stellate Cells Drives Liver Fibrosis and Diet-Induced Metabolic Dysfunction-Associated Steatohepatitis in Mice.

ABSTRACT: Liver fibrosis is a central feature of progressive liver diseases, including metabolic dysfunction-associated steatohepatitis (MASH). The profibrotic liver microenvironment drives hepatic stellate cell (HSC) activation and collagen deposition. However, the nature of HSC-mediated autocrine signaling during the fibrotic response has not been completely characterized. Here, we identify Netrin-1 as an autocrine factor that drives HSC activation and liver fibrosis in patients with MASH. Hepatic Netrin-1 expression was consistently elevated across multiple experimental models of liver fibrosis. Functional studies showed that adenovirus-associated virus (AAV)-mediated hepatic Netrin-1 overexpression exacerbated fibrosis, whereas HSC-specific conditional ablation of Netrin-1 markedly attenuated di

SUBMITTER: Zhao J 

PROVIDER: S-EPMC12915089 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature