Journal
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
Volume 235, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.ijbiomac.2023.123639
Keywords
Gomisin D; PDGFR ?; Hepatic stellate cells
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This study found that gomisin D can inhibit the activation of hepatic stellate cells (HSCs) by targeting PDGFR beta, thereby exerting anti-fibrotic effects in liver fibrosis.
Platelet-derived growth factor receptor beta (PDGFR beta) plays an important role in hepatic fibrosis and is closely associated with hepatic stellate cells (HSCs) activation. Previously, by modeling PDGFR beta affinity chromatog-raphy, we found that gomisin D can target PDGFR beta. However, whether gomisin D has anti-fibrosis effects through targeting PDGFR beta remained unclear. In this study, the effect of gomisin D on hepatic fibrosis was evaluated in vivo and vitro. HSC cell lines and primary HSC were cultured and functionally we found that gomisin D promotes HSC apoptosis, inhibits HSCs activation and proliferation. A male BALB/c mouse liver fibrosis model was established to comfirm gomisin D (especially in 50 mg/kg) could improve liver fibrosis by inhibiting HSCs activation. In addition, gomisin D had a good binding ability with PDGFR beta (KD = 3.3e-5 M). Mechanically, gomisin D regulated PDGF-BB/PDGFR beta signaling pathway by targeting PDGFR beta, further more inhibited HSC activation, subsequently inhibited inflammatory factors, ultimately improved CCl4-induced liver fibrosis. Overall, gomisin D could inhibit HSC proliferation and activation, promote HSC apoptosis, and alleviate CCl4- induced hepatic fibrosis by targeting PDGFR beta and regulating PDGF-BB/PDGFR beta signaling pathway. This study provides a new drug for anti-liver firbosis therapy, and elucidates the deeper mechanism of gomisin D against HSCs activation by targeting PDGFR beta.
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