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 |
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| 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) |
| Publisher Information: | MDPI AG, 2022. |
| Publication Year: | 2022 |
| Collection: | LCC:Organic chemistry |
| Subject Terms: | diabetic retinopathy, retinal pigment epithelial cells, galectin-1, OTX008, fibrosis, epithelial-mesenchymal transition, Organic chemistry, QD241-441 |
| More Details: | 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. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 27154785 1420-3049 |
| Relation: | https://www.mdpi.com/1420-3049/27/15/4785; https://doaj.org/toc/1420-3049 |
| DOI: | 10.3390/molecules27154785 |
| Access URL: | https://doaj.org/article/d3e4be0181bc4512aa6c567f2aa25e24 |
| Accession Number: | edsdoj.3e4be0181bc4512aa6c567f2aa25e24 |
| Database: | Directory of Open Access Journals |
| ISSN: | 27154785 14203049 |
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| DOI: | 10.3390/molecules27154785 |
| Published in: | Molecules |
| Language: | English |