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Effects of the Calix[4]arene Derivative Compound OTX008 on High Glucose-Stimulated ARPE-19 Cells: Focus on Galectin-1/TGF-β/EMT Pathway

Authors :
Maria Consiglia Trotta
Francesco Petrillo
Carlo Gesualdo
Settimio Rossi
Alberto Della Corte
Judit Váradi
Ferenc Fenyvesi
Michele D’Amico
Anca Hermenean
Source :
Molecules, Vol 27, Iss 15, p 4785 (2022)
Publication Year :
2022
Publisher :
MDPI AG, 2022.

Abstract

Diabetic retinopathy (DR) is a neurovascular disease characterized by the reduction of retina integrity and functionality, as a consequence of retinal pigment epithelial cell fibrosis. Although galectin-1 (a glycan-binding protein) has been associated with dysregulated retinal angiogenesis, no evidence has been reported about galectin-1 roles in DR-induced fibrosis. ARPE-19 cells were cultured in normal (5 mM) or high glucose (35 mM) for 3 days, then exposed to the selective galectin-1 inhibitor OTX008 (2.5–5–10 μM) for 6 days. The determination of cell viability and ROS content along with the analysis of specific proteins (by immunocytochemistry, Western blotting, and ELISA) or mRNAs (by real time-PCR) were performed. OTX008 5 μM and 10 μM improved cell viability and markedly reduced galectin-1 protein expression in cells exposed to high glucose. This was paralleled by a down-regulation of the TGF-β/, NF-kB p65 levels, and ROS content. Moreover, epithelial–mesenchymal transition markers were reduced by OTX008 5 μM and 10 μM. The inhibition of galectin-1 by OTX008 in DR may preserve retinal pigment epithelial cell integrity and functionality by reducing their pro-fibrotic phenotype and epithelial–mesenchymal transition phenomenon induced by diabetes.

Details

Language :
English
ISSN :
27154785 and 14203049
Volume :
27
Issue :
15
Database :
Directory of Open Access Journals
Journal :
Molecules
Publication Type :
Academic Journal
Accession number :
edsdoj.3e4be0181bc4512aa6c567f2aa25e24
Document Type :
article
Full Text :
https://doi.org/10.3390/molecules27154785