WISP1 and HMGB1 Coordinate Hepatocyte–Macrophage Inflammatory Communication and Macrophage Functional Remodeling During Sepsis-Induced Liver Injury

Sepsis induced liver injury involves abnormal activation of inflammatory signaling and immune dysfunction, but the mechanisms underlying intercellular regulation remain incompletely understood. Following cecal ligation and puncture, hepatic expression of WNT1-inducible signaling pathway protein 1 (WISP1) and high mobility group box 1 (HMGB1) was increased and accompanied by marked liver injury. Hepatocyte apoptosis increased from 3.26 in the Sham group to 11.39 in the Model group. Suppression of WISP1 or HMGB1 alleviated tissue injury, indicating that these molecules are associated with the progression of sepsis induced liver injury. Further analysis showed that WISP1 and HMGB1 related signaling was not merely associated with changes in inflammatory mediator expression, but also contributed to communication between hepatocytes and macrophages. Septic hepatocyte derived signals impaired macrophage autophagic flux, with Bafilomycin A1-sensitive accumulation of microtubule-associated protein 1 light chain 3-II (LC3-II) decreasing from 0.30 to 0.01, indicating that the inflammatory environment affected dynamic autophagic processing rather than simply altering LC3-II levels. Meanwhile, restoration of autophagy partially improved macrophage mitochondrial dysfunction and phenotypic alterations, suggesting that intracellular homeostasis may represent an important link between inflammatory signaling and immune functional remodeling. Collectively, this study identifies an association between WISP1/HMGB1 related inflammatory signaling, hepatocyte macrophage communication, autophagic homeostasis, and functional remodeling, providing new insights into the cellular regulation of sepsis induced liver injury.