Yuru ZHAI, Yan BAI, Yunyun LI. FGF2 Regulates Hypoxia-Induced Proliferation and Collagen Metabolism of Scleral Fibroblasts Through the PERK/EIF2α/ATF4 Signaling Pathway[J]. Journal of Kunming Medical University, 2024, 45(10): 22-28. doi: 10.12259/j.issn.2095-610X.S20241004
Citation: Yuru ZHAI, Yan BAI, Yunyun LI. FGF2 Regulates Hypoxia-Induced Proliferation and Collagen Metabolism of Scleral Fibroblasts Through the PERK/EIF2α/ATF4 Signaling Pathway[J]. Journal of Kunming Medical University, 2024, 45(10): 22-28. doi: 10.12259/j.issn.2095-610X.S20241004

FGF2 Regulates Hypoxia-Induced Proliferation and Collagen Metabolism of Scleral Fibroblasts Through the PERK/EIF2α/ATF4 Signaling Pathway

doi: 10.12259/j.issn.2095-610X.S20241004
  • Received Date: 2024-04-25
    Available Online: 2024-10-14
  • Publish Date: 2024-10-31
  •   Objectives  To investigate the effects of FGF2 on the proliferation and collagen production of hypoxia-induced scleral fibroblasts (SF) and explore the downstream signaling pathways it regulates.   Methods  5% O2 was used to stimulate the SF to induce myopia SF model for 24 hours. RT-qPCR was used to detect FGF2 mRNA expression, and Western blot analysis was used to check FGF2 protein expression. The Cell Counting Kit-8 (CCK-8), flow cytometry, and Western blot were used to assess cell proliferation vitality, cell apoptosis, and the expression of collagen metabolism-related proteins collagen I, MMP2, and pathway proteins PERK, p-PERK, EIF2α, EIF2α, and ATF4.   Results  Hypoxia increased FGF2 mRNA and protein expression (P < 0.01) , activated the PERK/EIF2α/ATF4 pathway (P < 0.001), inhibited SF cell proliferation (P < 0.001) and collagen I expression (P < 0.001), while induced MMP2 expression (P < 0.001) and apoptosis (P < 0.001). Knocking down FGF2 or treating with PERK inhibitor GSK2606414 reversed the effect of hypoxia on SF cells, increased cell proliferation (P < 0.001) and collagen Ⅰ expression (P < 0.01), and suppressed cell apoptosis (P < 0.01). Mechanism study revealed that FGF2 knockdown dampened the activation of PERK/EIF2α/ATF4 pathway.   Conclusion  FGF2 affects hypoxia-induced SF proliferation and collagen metabolism by regulating the activation of PERK/EIF2α/ATF4 signaling pathway.
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