Activation of the platelet-derived growth factor (PDGF)/PDGF beta receptor (PDGFβR) axis has a critical role in liver fibrosis. However, the mechanisms that regulate the PDGF signaling are yet to be elucidated. The present study demonstrates that paired related homeobox protein 1 (Prrx1) is involved in PDGF-dependent hepatic stellate cell (HSCs) migration via modulation of the expression of metalloproteinases MMP2 and MMP9. PDGF elevated the level of Prrx1 through the activation of ERK/Sp1 and PI3K/Akt/Ets1 pathways. In vivo, an adenoviral-mediated Prrx1 shRNA administration attenuated liver fibrosis in thioacetamide-induced fibrotic models. These studies reveal a role of Prrx1 as a modulator of PDGF-dependent signaling in HSCs, and inhibiting its expression may offer a therapeutic approach for hepatic fibrosis.
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Gong, J., Han, J., He, J., Liu, J., Han, P., Wang, Y., … Tian, D. (2017). Paired related homeobox protein 1 regulates PDGF-induced chemotaxis of hepatic stellate cells in liver fibrosis. Laboratory Investigation, 97(9), 1020–1032. https://doi.org/10.1038/labinvest.2017.65