Pathophysiological role of platelet-derived growth factors in chronic liver disease

Platelet-derived growth factor (PDGF) and its receptor (PDGFR) signaling serves as a central driver of hepatic stellate cell (HSC) activation and extracellular matrix deposition in chronic liver diseases.Upon ligand binding, PDGFR undergoes dimerization and autophosphorylation, initiating key intracellular signaling pathways including PI3K/Akt, MEK/ERK, PLCγ/IP3, and JAK/STAT.Although these pathways represent major therapeutic targets, the clinical translation of non-selective PDGF inhibitors, such as tyrosine kinase inhibitors, has been hindered by off-target toxicity and limited efficacy.This review delineates the isoform-specific roles of PDGF ligands and receptors in liver fibrosis pathogenesis.We examine this signaling axis across varying disease contexts, ranging from metabolic dysfunction-associated steatotic liver disease (MASLD) and alcoholic liver disease (ALD) to end-stage liver disease (ESLD).Furthermore, we discuss the cellular crosstalk among HSCs, Kupffer cells, and endothelial cells within the fibrotic microenvironment.Understanding the signaling mechanisms of PDGF/PDGFR may reveal novel therapeutic targets in chronic liver disease.