Hepatocyte Apolipoprotein J Accelerates Injury-induced Liver Fibrosis by Activation Signal Transducer and Activator of Transcription 3 Through Ranbp2 Mediated-SUMOylation.

ABSTRACT:

Background & aims

Dysregulation of the signal transducer and activator of transcription 3 (STAT3) signaling pathway is closely linked to redox homeostasis and exacerbates liver injury. Apolipoprotein J (ApoJ), a chaperone sensitive to redox changes. We aim to investigate how hepatocyte ApoJ regulates the STAT3 pathway to mediate paracrine signaling that activates hepatic stellate cells (HSCs).

Methods

We constructed ApoJ hepatocyte-specific knockout (ApoJ HKO) and overexpression mouse models and induced experimental liver fibrosis. The intercellular signaling between hepatocytes and HSCs was studied by treating HSCs with hepatocyte culture supernatants. Additionally, single-cell RNA sequencing datasets from patients with liver cirrhosis and healthy controls were analyzed.

SUBMITTER: Liu L 

PROVIDER: S-EPMC12391277 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature