Platelet-derived growth factor receptor α (PDGFRα), a tyrosine kinase receptor, 
is up-regulated in hepatic stellate cells (HSCs) during chronic liver injury. 
HSCs mediate hepatic fibrosis through their activation from a quiescent state 
partially in response to profibrotic growth factors. HSC activation entails 
enhanced expression of profibrotic genes, increase in proliferation, and 
increase in motility, which facilitates migration within the hepatic lobule. We 
show colocalization of PDGFRα in murine carbon tetrachloride, bile duct 
ligation, and 0.1% 3,5-diethoxycarbonyl-1,4-dihydrocollidine models of chronic 
liver injury, and investigate the role of PDGFRα on proliferation, profibrotic 
gene expression, and migration in primary human HSCs (HHSteCs) using the 
PDGFRα-specific inhibitory monoclonal antibody olaratumab. Although lacking any 
effects on HHSteC transdifferentiation assessed by gene expression of ACTA2, 
TGFB1, COL1A1, SYP1, and FN1, olaratumab specifically reduced HHSteC 
proliferation (AlamarBlue assay) and cell migration (transwell migration 
assays). Using phospho-specific antibodies, we show that olaratumab attenuates 
PDGFRα activation in response to PDGF-BB, and reduced phosphorylation of 
extracellular signal-regulated kinase 1 and 2, Elk-1, p38, Akt, focal adhesion 
kinase, mechanistic target of rapamycin, C10 regulator of kinase II, and C10 
regulator of kinase-like, suggesting that PDGFRα contributes to mitogenesis and 
actin reorganization through diverse downstream effectors. Our findings support 
a distinct contribution of PDGFRα signaling to HSC proliferation and migration 
and provide evidence that inhibition of PDGFRα signaling could alter the 
pathogenesis of hepatic fibrosis.