Cargando…
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...
Autores principales: | , , , , , , , , |
---|---|
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 |
_version_ | 1784758597109940224 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9332238 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT trottamariaconsiglia effectsofthecalix4arenederivativecompoundotx008onhighglucosestimulatedarpe19cellsfocusongalectin1tgfbemtpathway AT petrillofrancesco effectsofthecalix4arenederivativecompoundotx008onhighglucosestimulatedarpe19cellsfocusongalectin1tgfbemtpathway AT gesualdocarlo effectsofthecalix4arenederivativecompoundotx008onhighglucosestimulatedarpe19cellsfocusongalectin1tgfbemtpathway AT rossisettimio effectsofthecalix4arenederivativecompoundotx008onhighglucosestimulatedarpe19cellsfocusongalectin1tgfbemtpathway AT cortealbertodella effectsofthecalix4arenederivativecompoundotx008onhighglucosestimulatedarpe19cellsfocusongalectin1tgfbemtpathway AT varadijudit effectsofthecalix4arenederivativecompoundotx008onhighglucosestimulatedarpe19cellsfocusongalectin1tgfbemtpathway AT fenyvesiferenc effectsofthecalix4arenederivativecompoundotx008onhighglucosestimulatedarpe19cellsfocusongalectin1tgfbemtpathway AT damicomichele effectsofthecalix4arenederivativecompoundotx008onhighglucosestimulatedarpe19cellsfocusongalectin1tgfbemtpathway AT hermeneananca effectsofthecalix4arenederivativecompoundotx008onhighglucosestimulatedarpe19cellsfocusongalectin1tgfbemtpathway |