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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

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 evide...

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Autores principales: Trotta, Maria Consiglia, Petrillo, Francesco, Gesualdo, Carlo, Rossi, Settimio, Corte, Alberto Della, Váradi, Judit, Fenyvesi, Ferenc, D’Amico, Michele, Hermenean, Anca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9332238/
https://www.ncbi.nlm.nih.gov/pubmed/35897964
http://dx.doi.org/10.3390/molecules27154785
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author Trotta, Maria Consiglia
Petrillo, Francesco
Gesualdo, Carlo
Rossi, Settimio
Corte, Alberto Della
Váradi, Judit
Fenyvesi, Ferenc
D’Amico, Michele
Hermenean, Anca
author_facet Trotta, Maria Consiglia
Petrillo, Francesco
Gesualdo, Carlo
Rossi, Settimio
Corte, Alberto Della
Váradi, Judit
Fenyvesi, Ferenc
D’Amico, Michele
Hermenean, Anca
author_sort Trotta, Maria Consiglia
collection PubMed
description 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.
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spelling pubmed-93322382022-07-29 Effects of the Calix[4]arene Derivative Compound OTX008 on High Glucose-Stimulated ARPE-19 Cells: Focus on Galectin-1/TGF-β/EMT Pathway Trotta, Maria Consiglia Petrillo, Francesco Gesualdo, Carlo Rossi, Settimio Corte, Alberto Della Váradi, Judit Fenyvesi, Ferenc D’Amico, Michele Hermenean, Anca Molecules Article 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. MDPI 2022-07-26 /pmc/articles/PMC9332238/ /pubmed/35897964 http://dx.doi.org/10.3390/molecules27154785 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Trotta, Maria Consiglia
Petrillo, Francesco
Gesualdo, Carlo
Rossi, Settimio
Corte, Alberto Della
Váradi, Judit
Fenyvesi, Ferenc
D’Amico, Michele
Hermenean, Anca
Effects of the Calix[4]arene Derivative Compound OTX008 on High Glucose-Stimulated ARPE-19 Cells: Focus on Galectin-1/TGF-β/EMT Pathway
title Effects of the Calix[4]arene Derivative Compound OTX008 on High Glucose-Stimulated ARPE-19 Cells: Focus on Galectin-1/TGF-β/EMT Pathway
title_full Effects of the Calix[4]arene Derivative Compound OTX008 on High Glucose-Stimulated ARPE-19 Cells: Focus on Galectin-1/TGF-β/EMT Pathway
title_fullStr Effects of the Calix[4]arene Derivative Compound OTX008 on High Glucose-Stimulated ARPE-19 Cells: Focus on Galectin-1/TGF-β/EMT Pathway
title_full_unstemmed Effects of the Calix[4]arene Derivative Compound OTX008 on High Glucose-Stimulated ARPE-19 Cells: Focus on Galectin-1/TGF-β/EMT Pathway
title_short Effects of the Calix[4]arene Derivative Compound OTX008 on High Glucose-Stimulated ARPE-19 Cells: Focus on Galectin-1/TGF-β/EMT Pathway
title_sort effects of the calix[4]arene derivative compound otx008 on high glucose-stimulated arpe-19 cells: focus on galectin-1/tgf-β/emt pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9332238/
https://www.ncbi.nlm.nih.gov/pubmed/35897964
http://dx.doi.org/10.3390/molecules27154785
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