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Current Medicinal Chemistry

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ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

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Research Article

ERM Complex, A Therapeutic Target for Vascular Leakage Induced by Diabetes

Author(s): Olga Simó-Servat, Hugo Ramos, Patricia Bogdanov, Marta García-Ramírez, Jordi Huerta, Cristina Hernández and Rafael Simó*

Volume 29, Issue 12, 2022

Published on: 17 August, 2021

Page: [2189 - 2199] Pages: 11

DOI: 10.2174/0929867328666210526114417

Abstract

Background: Ezrin, radixin, and moesin (the ERM complex) interact directly with membrane proteins regulating their attachment to actin filaments. ERM protein activation modifies cytoskeleton organization and alters the endothelial barrier function, thus favoring vascular leakage. However, little is known regarding the role of ERM proteins in diabetic retinopathy (DR). Objective: This study aimed to examine whether overexpression of the ERM complex exists in db/db mice and its main regulating factors.

Methods: 9 male db/db mice and 9 male db/+ aged 14 weeks were analyzed. ERM proteins were assessed by western blot and by immunohistochemistry. Vascular leakage was determined by the Evans blue method. To assess ERM regulation, HRECs were cultured in a medium containing 5.5 mM D-glucose (mimicking physiological conditions) and 25 mM D-glucose (mimicking hyperglycemia that occurs in diabetic patients). Moreover, treatment with TNF-α, IL-1β, or VEGF was added to a high glucose condition. The expression of ERM proteins was quantified by RT-PCR. Cell permeability was evaluated by measuring movements of FITC-dextran.

Results: A significant increase of ERM in diabetic mice in comparison with non-diabetic mice was observed. A high glucose condition alone did not have any effect on ERM expression. However, TNF-α and IL-1β induced a significant increase in ERM proteins.

Conclusion: The increase of ERM proteins induced by diabetes could be one of the mechanisms involved in vascular leakage and could be considered as a therapeutic target. Moreover, the upregulation of the ERM complex by diabetes is induced by inflammatory mediators rather than by high glucose itself.

Keywords: Ezrin, radixin, moesin, diabetic retinopathy, retinal permeability, db/db mouse, human retinal endothelial cells.

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