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Sprouty-related proteins with EVH1 domain (SPRED2) prevents high-glucose induced endothelial–mesenchymal transition and endothelial injury by suppressing MAPK activation
Diabetic retinopathy (DR) is a common complication of diabetes, and the leading cause of blindness in adults. Sprouty-related proteins with EVH1 domain (SPRED2) play an important role in diabetes and are closely related to the lens and eye morphogenesis. This study attempted to investigate the role...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9275976/ https://www.ncbi.nlm.nih.gov/pubmed/35707829 http://dx.doi.org/10.1080/21655979.2022.2086351 |
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author | Liu, Tian Zhao, Jing Lin, Chengmin |
author_facet | Liu, Tian Zhao, Jing Lin, Chengmin |
author_sort | Liu, Tian |
collection | PubMed |
description | Diabetic retinopathy (DR) is a common complication of diabetes, and the leading cause of blindness in adults. Sprouty-related proteins with EVH1 domain (SPRED2) play an important role in diabetes and are closely related to the lens and eye morphogenesis. This study attempted to investigate the role and related mechanism of SPRED2 in DR. DR rat model was established by administration streptozocin. Human retinal endothelial cells (HRECs) were treated with high glucose (HG) to mimic DR. The results showed that SPRED2 expression was decreased in the retinal tissues of DR rats and HG-treated HRECs. MTT assay and flow cytometry data showed that SPRED2 overexpression reduced cell viability of HG-treated HRECs. SPRED2 overexpression enhanced Caspase-3 activity and promoted apoptosis of HG-treated HRECs. Furthermore, the expressions of endothelial cell markers CD31 and E-cad were down-regulated, whereas the expressions of mesenchymal cell markers FSP1, SM22, and α-SMA were up-regulated in the HG-treated HRECs. SPRED2 overexpression reversed HG-induced endothelial–mesenchymal transition in HRECs. The expressions of tight junction components claudin 3, occludin, and ZO-1 were increased in HG-treated HRECs following SPRED2 up-regulation. In addition, SPRED2 overexpression downregulated the expression of p-ERK1/2, p-p38, and p-JNK in the HG-treated HRECs. In conclusion, this study demonstrated that SPRED2 overexpression repressed endothelial–mesenchymal transition and endothelial injury in HG-treated HRECs by suppressing MAPK signaling pathway. These findings suggested that SPRED2 may be a novel potential therapeutic target implicated in DR progression. |
format | Online Article Text |
id | pubmed-9275976 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-92759762022-07-13 Sprouty-related proteins with EVH1 domain (SPRED2) prevents high-glucose induced endothelial–mesenchymal transition and endothelial injury by suppressing MAPK activation Liu, Tian Zhao, Jing Lin, Chengmin Bioengineered Research Paper Diabetic retinopathy (DR) is a common complication of diabetes, and the leading cause of blindness in adults. Sprouty-related proteins with EVH1 domain (SPRED2) play an important role in diabetes and are closely related to the lens and eye morphogenesis. This study attempted to investigate the role and related mechanism of SPRED2 in DR. DR rat model was established by administration streptozocin. Human retinal endothelial cells (HRECs) were treated with high glucose (HG) to mimic DR. The results showed that SPRED2 expression was decreased in the retinal tissues of DR rats and HG-treated HRECs. MTT assay and flow cytometry data showed that SPRED2 overexpression reduced cell viability of HG-treated HRECs. SPRED2 overexpression enhanced Caspase-3 activity and promoted apoptosis of HG-treated HRECs. Furthermore, the expressions of endothelial cell markers CD31 and E-cad were down-regulated, whereas the expressions of mesenchymal cell markers FSP1, SM22, and α-SMA were up-regulated in the HG-treated HRECs. SPRED2 overexpression reversed HG-induced endothelial–mesenchymal transition in HRECs. The expressions of tight junction components claudin 3, occludin, and ZO-1 were increased in HG-treated HRECs following SPRED2 up-regulation. In addition, SPRED2 overexpression downregulated the expression of p-ERK1/2, p-p38, and p-JNK in the HG-treated HRECs. In conclusion, this study demonstrated that SPRED2 overexpression repressed endothelial–mesenchymal transition and endothelial injury in HG-treated HRECs by suppressing MAPK signaling pathway. These findings suggested that SPRED2 may be a novel potential therapeutic target implicated in DR progression. Taylor & Francis 2022-06-15 /pmc/articles/PMC9275976/ /pubmed/35707829 http://dx.doi.org/10.1080/21655979.2022.2086351 Text en © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Paper Liu, Tian Zhao, Jing Lin, Chengmin Sprouty-related proteins with EVH1 domain (SPRED2) prevents high-glucose induced endothelial–mesenchymal transition and endothelial injury by suppressing MAPK activation |
title | Sprouty-related proteins with EVH1 domain (SPRED2) prevents high-glucose induced endothelial–mesenchymal transition and endothelial injury by suppressing MAPK activation |
title_full | Sprouty-related proteins with EVH1 domain (SPRED2) prevents high-glucose induced endothelial–mesenchymal transition and endothelial injury by suppressing MAPK activation |
title_fullStr | Sprouty-related proteins with EVH1 domain (SPRED2) prevents high-glucose induced endothelial–mesenchymal transition and endothelial injury by suppressing MAPK activation |
title_full_unstemmed | Sprouty-related proteins with EVH1 domain (SPRED2) prevents high-glucose induced endothelial–mesenchymal transition and endothelial injury by suppressing MAPK activation |
title_short | Sprouty-related proteins with EVH1 domain (SPRED2) prevents high-glucose induced endothelial–mesenchymal transition and endothelial injury by suppressing MAPK activation |
title_sort | sprouty-related proteins with evh1 domain (spred2) prevents high-glucose induced endothelial–mesenchymal transition and endothelial injury by suppressing mapk activation |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9275976/ https://www.ncbi.nlm.nih.gov/pubmed/35707829 http://dx.doi.org/10.1080/21655979.2022.2086351 |
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