2. Academic Validation
  3. Gomisin D alleviates liver fibrosis through targeting PDGFRβ in hepatic stellate cells

Gomisin D alleviates liver fibrosis through targeting PDGFRβ in hepatic stellate cells

  • Int J Biol Macromol. 2023 Apr 30:235:123639. doi: 10.1016/j.ijbiomac.2023.123639.
Rong Wang 1,  Fangbin Liu 2,  Panpan Chen 1,  Shengnan Li 1,  Yanqiu Gu 1,  Lei Wang 1,  Chun Chen 1,  Yongfang Yuan 3
Affiliations

Affiliations

  • 1 Department of Pharmacy, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, 280 Mohe Rd, Shanghai 201999, China.
  • 2 Department of Pharmacy, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, 280 Mohe Rd, Shanghai 201999, China; School of Medicine, Shanghai University, 99 Shangda Road, Baoshan District, Shanghai 200444, China.
  • 3 Department of Pharmacy, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, 280 Mohe Rd, Shanghai 201999, China. Electronic address: [email protected].
PMID: 36822287 DOI: 10.1016/j.ijbiomac.2023.123639
Abstract

Platelet-derived growth factor receptor β (PDGFRβ) plays an important role in hepatic fibrosis and is closely associated with hepatic stellate cells (HSCs) activation. Previously, by modeling PDGFRβ affinity chromatography, we found that gomisin D can target PDGFRβ. However, whether gomisin D has anti-fibrosis effects through targeting PDGFRβ 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 PDGFRβ (KD = 3.3e-5 M). Mechanically, gomisin D regulated PDGF-BB/PDGFRβ signaling pathway by targeting PDGFRβ, 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 PDGFRβ and regulating PDGF-BB/PDGFRβ 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 PDGFRβ.

Keywords

Gomisin D; Hepatic stellate cells; PDGFRβ.

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