miR-205-5p inhibits homocysteine-induced pulmonary microvascular endothelium dysfunction by targeting FOXO1
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 underly...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
China Science Publishing & Media Ltd.
2023-07-01
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| Series: | Acta Biochimica et Biophysica Sinica |
| Subjects: | |
| Online Access: | https://www.sciengine.com/doi/10.3724/abbs.2023127 |
| _version_ | 1797635905089961984 |
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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 | DOAJ |
| 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<sup>+/‒</sup> 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. |
| first_indexed | 2024-03-11T12:26:47Z |
| format | Article |
| id | doaj.art-7ad02fe4c6754599a1b9b8f68241392c |
| institution | Directory Open Access Journal |
| issn | 1672-9145 |
| language | English |
| last_indexed | 2024-03-11T12:26:47Z |
| publishDate | 2023-07-01 |
| publisher | China Science Publishing & Media Ltd. |
| record_format | Article |
| series | Acta Biochimica et Biophysica Sinica |
| spelling | doaj.art-7ad02fe4c6754599a1b9b8f68241392c2023-11-06T08:30:47ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452023-07-01551456146610.3724/abbs.202312720d259ccmiR-205-5p inhibits homocysteine-induced pulmonary microvascular endothelium dysfunction by targeting FOXO1Huang Xiaobo0Li Zhen1Zhang Ling2Yang Yali3Wang Yanjia4Li Sirui5Li Guizhong6Feng Huiping7Yang Xiaoling8["Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Ningxia Medical University (The First People′s Hospital of Yinchuan), Yinchuan 750001, China"]["NHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Yinchuan 750004, China","School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, China"]["Department of Pathology, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan 750004, China"]["Department of Pathology, General Hospital of Ningxia Medical University, Yinchuan 750004, China"]["NHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Yinchuan 750004, China"]["NHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Yinchuan 750004, China"]["NHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Yinchuan 750004, China"]["Ningxia Baoshihua Hospital, Yinchuan 750001, China"]["NHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Yinchuan 750004, China","School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, China"]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<sup>+/‒</sup> 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.https://www.sciengine.com/doi/10.3724/abbs.2023127homocysteinemiR-205-5pFOXO1DNA methylationpulmonary microvascular endothelial dysfunction |
| spellingShingle | 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 Acta Biochimica et Biophysica Sinica homocysteine miR-205-5p FOXO1 DNA methylation pulmonary microvascular endothelial dysfunction |
| title | miR-205-5p inhibits homocysteine-induced pulmonary microvascular endothelium dysfunction by targeting FOXO1 |
| title_full | miR-205-5p inhibits homocysteine-induced pulmonary microvascular endothelium dysfunction by targeting FOXO1 |
| title_fullStr | miR-205-5p inhibits homocysteine-induced pulmonary microvascular endothelium dysfunction by targeting FOXO1 |
| title_full_unstemmed | miR-205-5p inhibits homocysteine-induced pulmonary microvascular endothelium dysfunction by targeting FOXO1 |
| title_short | miR-205-5p inhibits homocysteine-induced pulmonary microvascular endothelium dysfunction by targeting FOXO1 |
| title_sort | mir 205 5p inhibits homocysteine induced pulmonary microvascular endothelium dysfunction by targeting foxo1 |
| topic | homocysteine miR-205-5p FOXO1 DNA methylation pulmonary microvascular endothelial dysfunction |
| url | https://www.sciengine.com/doi/10.3724/abbs.2023127 |
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