biostudies-literatureWang SNIDDK NIH HHSNIH R01e2405678https://www.ebi.ac.uk/biostudies/studies/S-EPMC11653607biostudies-literatureUnknown11(47)Stressed hepatocytes promote liver fibrosis through communications with hepatic stellate cells (HSCs) during chronic liver injury. However, intra-hepatocyte players that facilitate such cell-to-cell communications are largely undefined. It is previously reported that hepatocyte E4BP4 is potently induced by ER stress and hepatocyte deletion of E4bp4 protects mice from high-fat diet-induced liver steatosis. Here how hepatocyte E4bp4 deficiency impacts the activation of HSCs and the progression toward MASH-associated liver fibrosis is examined. Hepatic E4BP4 is increased in mouse models of NASH diet- or CCl4-induced liver fibrosis. Hepatocyte-specific E4bp4 deletion protected mice against NASH diet-induced liver injury, inflammation, and fibrosis without impacting liver steatosis. Hepatocyte Advanced science (Weinheim, Baden-Wurttemberg, Germany)OPN-Mediated Crosstalk Between Hepatocyte E4BP4 and Hepatic Stellate Cells Promotes MASH-Associated Liver Fibrosis.PMC11653607R01 DK121170P30 DK089503P30 DK020572R00 DK077449R01 DK099593DK121170.DK099593Zhang GWang SYang MGao JTong XYin LfalseOPN-Mediated Crosstalk Between Hepatocyte E4BP4 and Hepatic Stellate Cells Promotes MASH-Associated Liver Fibrosis.Stressed hepatocytes promote liver fibrosis through communications with hepatic stellate cells (HSCs) during chronic liver injury. However, intra-hepatocyte players that facilitate such cell-to-cell communications are largely undefined. It is previously reported that hepatocyte E4BP4 is potently induced by ER stress and hepatocyte deletion of E4bp4 protects mice from high-fat diet-induced liver steatosis. Here how hepatocyte E4bp4 deficiency impacts the activation of HSCs and the progression toward MASH-associated liver fibrosis is examined. Hepatic E4BP4 is increased in mouse models of NASH diet- or CCl4-induced liver fibrosis. Hepatocyte-specific E4bp4 deletion protected mice against NASH diet-induced liver injury, inflammation, and fibrosis without impacting liver steatosis. Hepatocyte 2024-01-01T00:00:00Z2024 Dec2026-06-01T17:38:18.105Z2025-04-04T21:43:59.368ZS-EPMC116536073947308110.1002/advs.202405678