Journal article
Erythropoietin maintains VE-cadherin expression and barrier function in experimental diabetic retinopathy via inhibiting VEGF/VEGFR2/Src signaling pathway
Life sciences (1973), Vol.259, 118273
15 Oct 2020
PMID: 32800831
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
To explore the mechanisms of erythropoietin (EPO)'s protection on inner blood-retinal barrier (iBRB) in experimental diabetic retinopathy.
Male SD rats were rendered diabetic with streptozotocin, followed by intravitreal injection of EPO. The permeability of iBRB was examined with fluorescein isothiocyanate (FITC)-dextran. Human retinal microvascular endothelial cells (HRMECs) and human umbilical vein endothelial cells (HUVECs) were treated with glyoxal and studied for cell viability and barrier function. The expressions of vascular endothelial (VE)-cadherin, Src kinase, vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR2) were analyzed with Western blot, ELISA, qPCR, or immunofluorescence.
VE-cadherin in rat retinas was down-regulated with diabetes progression. EPO treatment could increase VE-cadherin expression at week 8 and week 16. The expressions of p-Src and p-VE-cadherin were increased at week 2, while decreased at week 8 of diabetes; which were prevented by EPO. The leakage of FITC-dextran in 8-week diabetic rat retinas was ameliorated by EPO. In vitro results showed the expressions of VEGF, p-Src and p-VE-cadherin were increased significantly, accompanied with the decreased barrier function, which were prevented by EPO. Ranibizumab and CGP77675 also inhibited the glyoxal-induced phosphorylation of Src and VE-cadherin. Cellular fractionation showed EPO mitigated the VE-cadherin internalization in glyoxal-treated cells.
EPO maintained the expression of VE-cadherin in experimental diabetic retinopathy by inhibiting its phosphorylation and internalization through VEGF/VEGFR2/Src pathway, thus improved the integrity of iBRB.
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Details
- Title
- Erythropoietin maintains VE-cadherin expression and barrier function in experimental diabetic retinopathy via inhibiting VEGF/VEGFR2/Src signaling pathway
- Creators
- Dandan Liu - Shanghai Tenth People's HospitalHua Xu - Soochow UniversityChaoyang Zhang - Shanghai Tenth People's HospitalHai Xie - Shanghai Tenth People's HospitalQian Yang - Shanghai Tenth People's HospitalWeiye Li - Drexel UniversityHaibin Tian - Shanghai Tenth People's HospitalLixia Lu - Shanghai Tenth People's HospitalJing-Ying Xu - Shanghai Tenth People's HospitalGuoxu Xu - Department of Ophthalmology, the Second Affiliated Hospital of Soochow University, Suzhou, ChinaKun Liu - Shanghai Jiao Tong UniversityXiaodong Sun - Shanghai Jiao Tong UniversityGuo-Tong Xu - Second Affiliated Hospital of Soochow UniversityJingfa Zhang - Shanghai Tenth People's Hospital
- Publication Details
- Life sciences (1973), Vol.259, 118273
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Ophthalmology [Historical]
- Identifiers
- 991019167344404721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Medicine, Research & Experimental
- Pharmacology & Pharmacy