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miR-205-5p inhibits homocysteine-induced pulmonary microvascular endothelium dysfunction by targeting FOXO1: miR-205-5p inhibits pulmonary microvascular endothelial dysfunction

Homocysteine (Hcy) is a risk factor for multiple chronic diseases, and vascular endothelial cell injury has been regarded as the initiating step for this process. miRNAs are involved in Hcy-induced endothelial dysfunction, while the underlying mechanism and roles of miRNAs in pulmonary endothelial d...

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Autores principales: Huang, Xiaobo, Li, Zhen, Zhang, Ling, Yang, Yali, Wang, Yanjia, Li, Sirui, Li, Guizhong, Feng, Huiping, Yang, Xiaoling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10520487/
https://www.ncbi.nlm.nih.gov/pubmed/37491880
http://dx.doi.org/10.3724/abbs.2023127
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author Huang, Xiaobo
Li, Zhen
Zhang, Ling
Yang, Yali
Wang, Yanjia
Li, Sirui
Li, Guizhong
Feng, Huiping
Yang, Xiaoling
author_facet Huang, Xiaobo
Li, Zhen
Zhang, Ling
Yang, Yali
Wang, Yanjia
Li, Sirui
Li, Guizhong
Feng, Huiping
Yang, Xiaoling
author_sort Huang, Xiaobo
collection PubMed
description Homocysteine (Hcy) is a risk factor for multiple chronic diseases, and vascular endothelial cell injury has been regarded as the initiating step for this process. miRNAs are involved in Hcy-induced endothelial dysfunction, while the underlying mechanism and roles of miRNAs in pulmonary endothelial dysfunction induced by homocysteine are unknown. Here, we find that miR-205-5p alleviates pulmonary endothelial dysfunction by targeting FOXO1 in CBS (+/‒) mice to protect against Hcy-induced pulmonary endothelial dysfunction. Mechanistically, we show that Hcy can lead to DNA hypermethylation of the miR-205-5p promoter due to the increased binding of DNMT1 to its promoter, which contributes to reduction of miR-205-5p expression. In summary, miR-205-5p promoter hypermethylation causes downregulation of miR-205-5p expression, resulting in a reduction in miR-205-5p binding to FOXO1 during homocysteine-induced pulmonary endothelial dysfunction. Our data indicate that miR-205-5p may be a potential therapeutic target against Hcy-induced pulmonary injury.
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spelling pubmed-105204872023-09-27 miR-205-5p inhibits homocysteine-induced pulmonary microvascular endothelium dysfunction by targeting FOXO1: miR-205-5p inhibits pulmonary microvascular endothelial dysfunction Huang, Xiaobo Li, Zhen Zhang, Ling Yang, Yali Wang, Yanjia Li, Sirui Li, Guizhong Feng, Huiping Yang, Xiaoling Acta Biochim Biophys Sin (Shanghai) Research Article Homocysteine (Hcy) is a risk factor for multiple chronic diseases, and vascular endothelial cell injury has been regarded as the initiating step for this process. miRNAs are involved in Hcy-induced endothelial dysfunction, while the underlying mechanism and roles of miRNAs in pulmonary endothelial dysfunction induced by homocysteine are unknown. Here, we find that miR-205-5p alleviates pulmonary endothelial dysfunction by targeting FOXO1 in CBS (+/‒) mice to protect against Hcy-induced pulmonary endothelial dysfunction. Mechanistically, we show that Hcy can lead to DNA hypermethylation of the miR-205-5p promoter due to the increased binding of DNMT1 to its promoter, which contributes to reduction of miR-205-5p expression. In summary, miR-205-5p promoter hypermethylation causes downregulation of miR-205-5p expression, resulting in a reduction in miR-205-5p binding to FOXO1 during homocysteine-induced pulmonary endothelial dysfunction. Our data indicate that miR-205-5p may be a potential therapeutic target against Hcy-induced pulmonary injury. Oxford University Press 2023-07-25 /pmc/articles/PMC10520487/ /pubmed/37491880 http://dx.doi.org/10.3724/abbs.2023127 Text en © The Author(s) 2021. 0 https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Article
Huang, Xiaobo
Li, Zhen
Zhang, Ling
Yang, Yali
Wang, Yanjia
Li, Sirui
Li, Guizhong
Feng, Huiping
Yang, Xiaoling
miR-205-5p inhibits homocysteine-induced pulmonary microvascular endothelium dysfunction by targeting FOXO1: miR-205-5p inhibits pulmonary microvascular endothelial dysfunction
title miR-205-5p inhibits homocysteine-induced pulmonary microvascular endothelium dysfunction by targeting FOXO1: miR-205-5p inhibits pulmonary microvascular endothelial dysfunction
title_full miR-205-5p inhibits homocysteine-induced pulmonary microvascular endothelium dysfunction by targeting FOXO1: miR-205-5p inhibits pulmonary microvascular endothelial dysfunction
title_fullStr miR-205-5p inhibits homocysteine-induced pulmonary microvascular endothelium dysfunction by targeting FOXO1: miR-205-5p inhibits pulmonary microvascular endothelial dysfunction
title_full_unstemmed miR-205-5p inhibits homocysteine-induced pulmonary microvascular endothelium dysfunction by targeting FOXO1: miR-205-5p inhibits pulmonary microvascular endothelial dysfunction
title_short miR-205-5p inhibits homocysteine-induced pulmonary microvascular endothelium dysfunction by targeting FOXO1: miR-205-5p inhibits pulmonary microvascular endothelial dysfunction
title_sort mir-205-5p inhibits homocysteine-induced pulmonary microvascular endothelium dysfunction by targeting foxo1: mir-205-5p inhibits pulmonary microvascular endothelial dysfunction
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10520487/
https://www.ncbi.nlm.nih.gov/pubmed/37491880
http://dx.doi.org/10.3724/abbs.2023127
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