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Pei LI, Jing ZHOU, Jiaqin CHEN. EGFL7 Inhibits the Sestrin2/Nrf2 Signaling Pathway,promotes Angiogenesis,and aggravates Diabetic Retinopathy in Rats[J]. Journal of Kunming Medical University.
Citation: Pei LI, Jing ZHOU, Jiaqin CHEN. EGFL7 Inhibits the Sestrin2/Nrf2 Signaling Pathway,promotes Angiogenesis,and aggravates Diabetic Retinopathy in Rats[J]. Journal of Kunming Medical University.

EGFL7 Inhibits the Sestrin2/Nrf2 Signaling Pathway,promotes Angiogenesis,and aggravates Diabetic Retinopathy in Rats

  • Received Date: 2025-09-18
    Available Online: 2026-01-03
  •   Objective   To investigate the impact of epidermal growth factor-like domain 7 (EGFL7) on angiogenesis in diabetic retinopathy, based on the Sestrin2/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway.   Methods   A diabetic retinopathy model was established in the rats. Retinal pathological morphology was examined using hematoxylin-eosin (HE) staining, while retinal vascular morphology was assessed via the retinal trypsin digestion assay. The mRNA expression levels of EGFL7, Sestrin2, Nrf2, and heme oxygenase-1 (HO-1) in retinal tissues were analyzed by RT-qPCR. Protein expression levels of EGFL7, Sestrin2, cluster of differentiation 31 (CD31), vascular endothelial growth factor receptor 2 (VEGFR2), Nrf2, and HO-1 were detected by Western blot. Corresponding assay kits were used to measure the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) in the intraocular aqueous humor.   Results   Compared with the control group, rats in the model group exhibited pathological damage in retinal tissues, increased retinal vascular density, and elevated levels of EGFL7, CD31, VEGFR2, and MDA (P < 0.05), whereas levels of SOD, GSH-Px, Sestrin2, Nrf2, and HO-1 were decreased (P < 0.05). No significant changes were observed in the above pathological indicators in the IgG group compared with the model group (P > 0.05). In contrast, compared with the IgG group, rats in the anti-EGFL7 group showed alleviated retinal pathological injury, reduced retinal vascular density, decreased levels of EGFL7, CD31, VEGFR2, and MDA (P < 0.05), and increased levels of SOD, GSH-Px, Sestrin2, Nrf2, and HO-1 (P < 0.05).   Conclusion   EGFL7 may exacerbate retinal neovascularization in diabetic retinopathy rats by promoting oxidative stress, a mechanism potentially associated with the inhibition of the Sestrin2/Nrf2 signaling pathway.
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