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VEGF Mediates Retinal Müller Cell Viability and Neuroprotection through BDNF in Diabetes
To investigate the mechanism of vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF) in Müller cell (MC) viability and neuroprotection in diabetic retinopathy (DR), we examined the role of VEGF in MC viability and BDNF production, and the effect of BDNF on MC viabil...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150851/ https://www.ncbi.nlm.nih.gov/pubmed/34068807 http://dx.doi.org/10.3390/biom11050712 |
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author | Le, Yun-Zheng Xu, Bei Chucair-Elliott, Ana J. Zhang, Huiru Zhu, Meili |
author_facet | Le, Yun-Zheng Xu, Bei Chucair-Elliott, Ana J. Zhang, Huiru Zhu, Meili |
author_sort | Le, Yun-Zheng |
collection | PubMed |
description | To investigate the mechanism of vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF) in Müller cell (MC) viability and neuroprotection in diabetic retinopathy (DR), we examined the role of VEGF in MC viability and BDNF production, and the effect of BDNF on MC viability under diabetic conditions. Mouse primary MCs and cells of a rat MC line, rMC1, were used in investigating MC viability and BDNF production under diabetic conditions. VEGF-stimulated BDNF production was confirmed in mice. The mechanism of BDNF-mediated MC viability was examined using siRNA knockdown. Under diabetic conditions, recombinant VEGF (rVEGF) stimulated MC viability and BDNF production in a dose-dependent manner. rBDNF also supported MC viability in a dose-dependent manner. Targeting BDNF receptor tropomyosin receptor kinase B (TRK-B) with siRNA knockdown substantially downregulated the activated (phosphorylated) form of serine/threonine-specific protein kinase (AKT) and extracellular signal-regulated kinase (ERK), classical survival and proliferation mediators. Finally, the loss of MC viability in TrkB siRNA transfected cells under diabetic conditions was rescued by rBDNF. Our results provide direct evidence that VEGF is a positive regulator for BDNF production in diabetes for the first time. This information is essential for developing BDNF-mediated neuroprotection in DR and hypoxic retinal diseases, and for improving anti-VEGF treatment for these blood–retina barrier disorders, in which VEGF is a major therapeutic target for vascular abnormalities. |
format | Online Article Text |
id | pubmed-8150851 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-81508512021-05-27 VEGF Mediates Retinal Müller Cell Viability and Neuroprotection through BDNF in Diabetes Le, Yun-Zheng Xu, Bei Chucair-Elliott, Ana J. Zhang, Huiru Zhu, Meili Biomolecules Article To investigate the mechanism of vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF) in Müller cell (MC) viability and neuroprotection in diabetic retinopathy (DR), we examined the role of VEGF in MC viability and BDNF production, and the effect of BDNF on MC viability under diabetic conditions. Mouse primary MCs and cells of a rat MC line, rMC1, were used in investigating MC viability and BDNF production under diabetic conditions. VEGF-stimulated BDNF production was confirmed in mice. The mechanism of BDNF-mediated MC viability was examined using siRNA knockdown. Under diabetic conditions, recombinant VEGF (rVEGF) stimulated MC viability and BDNF production in a dose-dependent manner. rBDNF also supported MC viability in a dose-dependent manner. Targeting BDNF receptor tropomyosin receptor kinase B (TRK-B) with siRNA knockdown substantially downregulated the activated (phosphorylated) form of serine/threonine-specific protein kinase (AKT) and extracellular signal-regulated kinase (ERK), classical survival and proliferation mediators. Finally, the loss of MC viability in TrkB siRNA transfected cells under diabetic conditions was rescued by rBDNF. Our results provide direct evidence that VEGF is a positive regulator for BDNF production in diabetes for the first time. This information is essential for developing BDNF-mediated neuroprotection in DR and hypoxic retinal diseases, and for improving anti-VEGF treatment for these blood–retina barrier disorders, in which VEGF is a major therapeutic target for vascular abnormalities. MDPI 2021-05-10 /pmc/articles/PMC8150851/ /pubmed/34068807 http://dx.doi.org/10.3390/biom11050712 Text en © 2021 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 Le, Yun-Zheng Xu, Bei Chucair-Elliott, Ana J. Zhang, Huiru Zhu, Meili VEGF Mediates Retinal Müller Cell Viability and Neuroprotection through BDNF in Diabetes |
title | VEGF Mediates Retinal Müller Cell Viability and Neuroprotection through BDNF in Diabetes |
title_full | VEGF Mediates Retinal Müller Cell Viability and Neuroprotection through BDNF in Diabetes |
title_fullStr | VEGF Mediates Retinal Müller Cell Viability and Neuroprotection through BDNF in Diabetes |
title_full_unstemmed | VEGF Mediates Retinal Müller Cell Viability and Neuroprotection through BDNF in Diabetes |
title_short | VEGF Mediates Retinal Müller Cell Viability and Neuroprotection through BDNF in Diabetes |
title_sort | vegf mediates retinal müller cell viability and neuroprotection through bdnf in diabetes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150851/ https://www.ncbi.nlm.nih.gov/pubmed/34068807 http://dx.doi.org/10.3390/biom11050712 |
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