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

Yuru ZHAI; Yan BAI; Yunyun LI

doi:10.12259/j.issn.2095-610X.S20241004

Volume 45 Issue 10

Oct. 2024

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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

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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

Dept. of Ophthalmology，Changzhi People’s Hospital，Changzhi Shanxi 046000，China

Received Date: 2024-04-25
Available Online: 2024-10-14
Publish Date: 2024-10-31

Abstract

Abstract

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.
- Scleral fibroblasts,
- Hypoxia,
- FGF2,
- Proliferation,
- Collagen metabolism

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References

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