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.