Human plasminogen-derived N-acetyl-Arg-Leu-Tyr-Glu antagonizes VEGFR-2 to prevent blood-retinal barrier breakdown in diabetic mice

Wonjin Park, Joohwan Kim, Seunghwan Choi, Taesam Kim, Minsik Park, Suji Kim, Ji Chang You, Jeong Hun Kim, Kwon Soo Ha, Jeong Hyung Lee, Young Guen Kwon, Young Myeong Kim

Research output: Contribution to journalArticlepeer-review

Abstract

Targeting the vascular endothelial growth factor (VEGF)/its receptor-2 (VEGFR-2) system has become a mainstay of treatment for many human diseases, including retinal diseases. We examined the therapeutic effect of recently developed N-acetylated Arg-Leu-Tyr-Glu (Ac-RLYE), a human plasminogen kringle-5 domain-derived VEGFR-2 antagonists, on the pathogenesis of diabetic retinopathy. Ac-RLYE inhibited VEGF-A-mediated VEGFR-2 activation and endothelial nitric oxide synthase (eNOS)-derived NO production in the retinas of diabetic mice. In addition, Ac-RLYE prevented the disruption of adherens and tight junctions and vascular leakage by inhibiting S-nitrosylation of β-catenin and tyrosine nitration of p190RhoGAP in the retinal vasculature of diabetic mice. Peptide treatment preserved the pericyte coverage of retinal capillaries by upregulating angiopoietin-2. These results suggest that Ac-RLYE potentially prevents blood-retinal barrier breakdown and vascular leakage by antagonizing VEGFR-2; Ac-RLYE can be used as a potential therapeutic drug for the treatment of diabetic retinopathy.

Original languageEnglish
Article number111110
JournalBiomedicine and Pharmacotherapy
Volume134
DOIs
Publication statusPublished - 2021 Feb

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) grants funded by the Korea Government ( 2017R1A2B300456514 and 2020R1A5A8019180 ).

Publisher Copyright:
© 2020 The Authors

All Science Journal Classification (ASJC) codes

  • Pharmacology

Fingerprint

Dive into the research topics of 'Human plasminogen-derived N-acetyl-Arg-Leu-Tyr-Glu antagonizes VEGFR-2 to prevent blood-retinal barrier breakdown in diabetic mice'. Together they form a unique fingerprint.

Cite this