Title:ERM Complex, A Therapeutic Target for Vascular Leakage Induced
by Diabetes
Volume: 29
Issue: 12
Author(s): Olga Simó-Servat, Hugo Ramos, Patricia Bogdanov, Marta García-Ramírez, Jordi Huerta, Cristina Hernández and Rafael Simó*
Affiliation:
- Diabetes and Metabolism Research Unit, Vall d’Hebron Research Institute, Universitat Autònoma de Barcelona, 08035 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades
Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ICSIII), 28029 Madrid, Spain
Keywords:
Ezrin, radixin, moesin, diabetic retinopathy, retinal permeability, db/db mouse, human retinal endothelial cells.
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.
