Signaling

Zonation gradients (Wnt, oxygen, bile acids) control hepatocyte gene programs via spatially restricted transcription factor activity; therapeutic window differs by zone.

LSEC-derived FGF1 signals to pericentral hepatocytes via FGFR4 to suppress lipid accumulation; retinoic acid receptor RXRG controls this paracrine axis.

Nr1i3 (CAR nuclear receptor) and Nfix regulate pericentral gene programs; Wnt-driven Nr1i3 expression is the mechanistic link between Wnt gradient and Zone 3 metabolic identity.

Albumin level functions as a paracrine sensor of hepatic mass; signals HSCs to gate regenerative response via an albumin-sensing mechanism.

EGFR-mediated signalling separates hepatocyte proliferation from lipid accumulation after partial hepatectomy; keeping the two programs apart accelerates regeneration and reduces post-operative liver failure.

STING acts as an organelle-stress checkpoint in hepatocytes: sensing mitochondrial and ER damage, it drives fate decisions between survival, pyroptosis, and fibrogenic remodeling. Positions STING as a target beyond antiviral defense.

Bidirectional paracrine signaling between hepatocytes and HSCs in fibrosis: hepatocyte-derived TGF-beta, PDGF, and lipid mediators activate HSCs; activated HSCs return pro-fibrotic and pro-apoptotic signals to hepatocytes.

Ubiquitin-proteasome dysregulation in hepatocytes links metabolic stress, innate immune activation, and cell fate decisions across MASLD, viral hepatitis, and HCC; proposes ubiquitin axis as a convergence point.

Plasma IL-13 rises after weight loss in severe obesity; in mice and primary hepatocytes IL-13 limits triglyceride accumulation through IL-13Ra1, JNK and FOSL2. Human cohort plus mouse; single study.

LSEC-secreted HGF suppresses HBV replication in adjacent hepatocytes via paracrine signaling; disrupting this LSEC-to-hepatocyte axis elevates viral replication in cell-based models. Cell model; single study.