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Activated cGAS/STING signaling elicits endothelial cell senescence in early diabetic retinopathy

Diabetic retinopathy (DR) is a leading cause of blindness in working-age adults and remains an important public health issue worldwide. Here we demonstrate that the expression of stimulator of interferon genes (STING) is increased in patients with DR and animal models of diabetic eye disease. STING...

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Autores principales: Liu, Haitao, Ghosh, Sayan, Vaidya, Tanuja, Bammidi, Sridhar, Huang, Chao, Shang, Peng, Nair, Archana Padmanabhan, Chowdhury, Olivia, Stepicheva, Nadezda A., Strizhakova, Anastasia, Hose, Stacey, Mitrousis, Nikolaos, Gadde, Santosh Gopikrishna, MB, Thirumalesh, Strassburger, Pamela, Widmer, Gabriella, Lad, Eleonora M., Fort, Patrice E., Sahel, José-Alain, Zigler, J. Samuel, Sethu, Swaminathan, Westenskow, Peter D., Proia, Alan D., Sodhi, Akrit, Ghosh, Arkasubhra, Feenstra, Derrick, Sinha, Debasish
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10371250/
https://www.ncbi.nlm.nih.gov/pubmed/37345657
http://dx.doi.org/10.1172/jci.insight.168945
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author Liu, Haitao
Ghosh, Sayan
Vaidya, Tanuja
Bammidi, Sridhar
Huang, Chao
Shang, Peng
Nair, Archana Padmanabhan
Chowdhury, Olivia
Stepicheva, Nadezda A.
Strizhakova, Anastasia
Hose, Stacey
Mitrousis, Nikolaos
Gadde, Santosh Gopikrishna
MB, Thirumalesh
Strassburger, Pamela
Widmer, Gabriella
Lad, Eleonora M.
Fort, Patrice E.
Sahel, José-Alain
Zigler, J. Samuel
Sethu, Swaminathan
Westenskow, Peter D.
Proia, Alan D.
Sodhi, Akrit
Ghosh, Arkasubhra
Feenstra, Derrick
Sinha, Debasish
author_facet Liu, Haitao
Ghosh, Sayan
Vaidya, Tanuja
Bammidi, Sridhar
Huang, Chao
Shang, Peng
Nair, Archana Padmanabhan
Chowdhury, Olivia
Stepicheva, Nadezda A.
Strizhakova, Anastasia
Hose, Stacey
Mitrousis, Nikolaos
Gadde, Santosh Gopikrishna
MB, Thirumalesh
Strassburger, Pamela
Widmer, Gabriella
Lad, Eleonora M.
Fort, Patrice E.
Sahel, José-Alain
Zigler, J. Samuel
Sethu, Swaminathan
Westenskow, Peter D.
Proia, Alan D.
Sodhi, Akrit
Ghosh, Arkasubhra
Feenstra, Derrick
Sinha, Debasish
author_sort Liu, Haitao
collection PubMed
description Diabetic retinopathy (DR) is a leading cause of blindness in working-age adults and remains an important public health issue worldwide. Here we demonstrate that the expression of stimulator of interferon genes (STING) is increased in patients with DR and animal models of diabetic eye disease. STING has been previously shown to regulate cell senescence and inflammation, key contributors to the development and progression of DR. To investigate the mechanism whereby STING contributes to the pathogenesis of DR, diabetes was induced in STING-KO mice and STING(GT) (loss-of-function mutation) mice, and molecular alterations and pathological changes in the retina were characterized. We report that retinal endothelial cell senescence, inflammation, and capillary degeneration were all inhibited in STING-KO diabetic mice; these observations were independently corroborated in STING(GT) mice. These protective effects resulted from the reduction in TBK1, IRF3, and NF-κB phosphorylation in the absence of STING. Collectively, our results suggest that targeting STING may be an effective therapy for the early prevention and treatment of DR.
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spelling pubmed-103712502023-07-27 Activated cGAS/STING signaling elicits endothelial cell senescence in early diabetic retinopathy Liu, Haitao Ghosh, Sayan Vaidya, Tanuja Bammidi, Sridhar Huang, Chao Shang, Peng Nair, Archana Padmanabhan Chowdhury, Olivia Stepicheva, Nadezda A. Strizhakova, Anastasia Hose, Stacey Mitrousis, Nikolaos Gadde, Santosh Gopikrishna MB, Thirumalesh Strassburger, Pamela Widmer, Gabriella Lad, Eleonora M. Fort, Patrice E. Sahel, José-Alain Zigler, J. Samuel Sethu, Swaminathan Westenskow, Peter D. Proia, Alan D. Sodhi, Akrit Ghosh, Arkasubhra Feenstra, Derrick Sinha, Debasish JCI Insight Research Article Diabetic retinopathy (DR) is a leading cause of blindness in working-age adults and remains an important public health issue worldwide. Here we demonstrate that the expression of stimulator of interferon genes (STING) is increased in patients with DR and animal models of diabetic eye disease. STING has been previously shown to regulate cell senescence and inflammation, key contributors to the development and progression of DR. To investigate the mechanism whereby STING contributes to the pathogenesis of DR, diabetes was induced in STING-KO mice and STING(GT) (loss-of-function mutation) mice, and molecular alterations and pathological changes in the retina were characterized. We report that retinal endothelial cell senescence, inflammation, and capillary degeneration were all inhibited in STING-KO diabetic mice; these observations were independently corroborated in STING(GT) mice. These protective effects resulted from the reduction in TBK1, IRF3, and NF-κB phosphorylation in the absence of STING. Collectively, our results suggest that targeting STING may be an effective therapy for the early prevention and treatment of DR. American Society for Clinical Investigation 2023-06-22 /pmc/articles/PMC10371250/ /pubmed/37345657 http://dx.doi.org/10.1172/jci.insight.168945 Text en © 2023 Liu et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Liu, Haitao
Ghosh, Sayan
Vaidya, Tanuja
Bammidi, Sridhar
Huang, Chao
Shang, Peng
Nair, Archana Padmanabhan
Chowdhury, Olivia
Stepicheva, Nadezda A.
Strizhakova, Anastasia
Hose, Stacey
Mitrousis, Nikolaos
Gadde, Santosh Gopikrishna
MB, Thirumalesh
Strassburger, Pamela
Widmer, Gabriella
Lad, Eleonora M.
Fort, Patrice E.
Sahel, José-Alain
Zigler, J. Samuel
Sethu, Swaminathan
Westenskow, Peter D.
Proia, Alan D.
Sodhi, Akrit
Ghosh, Arkasubhra
Feenstra, Derrick
Sinha, Debasish
Activated cGAS/STING signaling elicits endothelial cell senescence in early diabetic retinopathy
title Activated cGAS/STING signaling elicits endothelial cell senescence in early diabetic retinopathy
title_full Activated cGAS/STING signaling elicits endothelial cell senescence in early diabetic retinopathy
title_fullStr Activated cGAS/STING signaling elicits endothelial cell senescence in early diabetic retinopathy
title_full_unstemmed Activated cGAS/STING signaling elicits endothelial cell senescence in early diabetic retinopathy
title_short Activated cGAS/STING signaling elicits endothelial cell senescence in early diabetic retinopathy
title_sort activated cgas/sting signaling elicits endothelial cell senescence in early diabetic retinopathy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10371250/
https://www.ncbi.nlm.nih.gov/pubmed/37345657
http://dx.doi.org/10.1172/jci.insight.168945
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