Neutrophil extracellular traps-triggered hepatocellular senescence exacerbates lipotoxicity in non-alcoholic steatohepatitis.

ABSTRACT:

Introduction

Neutrophils are initial responders in inflammation and contribute to non-alcoholic fatty liver disease (NAFLD) progression to steatohepatitis (NASH). Neutrophil extracellular traps (NETs) are implicated in liver injury, yet their precise mechanisms in NASH progression remains unclear.

Objectives

This study investigates how NETs drive NASH progression by exacerbating hepatocyte lipotoxicity and explore the regulatory mechanism of NETs formation and its downstream effects on liver pathology.

Methods

Clinical samples from NASH patients and diet-induced NASH mice were analyzed for NET levels. NETs were pharmacologically inhibited, and senescent cells were selectively eliminated in mice. Myeloid-specific RBP-J knockout mice were generated to disrupt Notch sign

SUBMITTER: Xu M 

PROVIDER: S-EPMC12766193 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature