TGF-βR/PDGFRα signaling cross talk in HSC. Ligand-dependent and -independent signaling pathways are shown. During ligand-independent signaling, PDGFRα is recruited to TβRI/TβRII complexes by TGF-β stimulation. Through interaction with TβRII, PDGFRα promotes internalization and trafficking of TGF-β receptors into the early endosomes, where phosphorylation of SMADs occurs and TGF-β signaling is activated. Knockdown of PDGFRα blocks endocytosis of TGF-β receptors, thereby inhibiting phosphorylation of SMADs. Activation of SMAD2/3 has been shown to lead to the upregulation of PDGF-A mRNA, which may indicate an autocrine mechanism of PDGFRα activation in HSCs. Abbreviations: TGF-β receptor II (TβRII). Adapted from Liu et al. (53).