Role of miR‐21‐5p/FilGAP axis in estradiol alleviating the progression of monocrotaline‐induced pulmonary hypertension
Abstract Background Aberrant expression of microRNAs (miRNAs) has been associated with the pathogenesis of pulmonary hypertension (PH). It is, however, not clear whether miRNAs are involved in estrogen rescue of PH. Methods Fresh plasma samples were prepared from 12 idiopathic pulmonary arterial hyp...
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| Format: | Article |
| Language: | English |
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Wiley
2022-06-01
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| Series: | Animal Models and Experimental Medicine |
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| Online Access: | https://doi.org/10.1002/ame2.12253 |
| _version_ | 1818500245149974528 |
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| author | Xiaoyi Hu Qian Wang Hui Zhao Wenhui Wu Qinhua Zhao Rong Jiang Jinming Liu Lan Wang Ping Yuan |
| author_facet | Xiaoyi Hu Qian Wang Hui Zhao Wenhui Wu Qinhua Zhao Rong Jiang Jinming Liu Lan Wang Ping Yuan |
| author_sort | Xiaoyi Hu |
| collection | DOAJ |
| description | Abstract Background Aberrant expression of microRNAs (miRNAs) has been associated with the pathogenesis of pulmonary hypertension (PH). It is, however, not clear whether miRNAs are involved in estrogen rescue of PH. Methods Fresh plasma samples were prepared from 12 idiopathic pulmonary arterial hypertension (IPAH) patients and 12 healthy controls undergoing right heart catheterization in Shanghai Pulmonary Hospital. From each sample, 5 μg of total RNA was tagged and hybridized on microRNA microarray chips. Monocrotaline‐induced PH (MCT‐PH) male rats were treated with 17β‐estradiol (E2) or vehicle. Subgroups were cotreated with estrogen receptor (ER) antagonist or with antagonist of miRNA. Results Many circulating miRNAs, including miR‐21‐5p and miR‐574‐5p, were markedly expressed in patients and of interest in predicting mean pulmonary arterial pressure elevation in patients. The expression of miR‐21‐5p in the lungs was significantly upregulated in MCT‐PH rats compared with the controls. However, miR‐574‐5p showed no difference in the lungs of MCT‐PH rats and controls. miR‐21‐5p was selected for further analysis in rats as E2 strongly regulated it. E2 decreased miR‐21‐5p expression in the lungs of MCT‐PH rats by ERβ. E2 reversed miR‐21‐5p target gene FilGAP downregulation in the lungs of MCT‐PH rats. The abnormal expression of RhoA, ROCK2, Rac1 and c‐Jun in the lungs of MCT‐PH rats was inhibited by E2 and miR‐21‐5p antagonist. Conclusions miR‐21‐5p level was remarkably associated with PH severity in patients. Moreover, the miR‐21‐5p/FilGAP signaling pathway modulated the protective effect of E2 on MCT‐PH through ERβ. |
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| institution | Directory Open Access Journal |
| issn | 2576-2095 |
| language | English |
| last_indexed | 2024-12-10T20:40:09Z |
| publishDate | 2022-06-01 |
| publisher | Wiley |
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| series | Animal Models and Experimental Medicine |
| spelling | doaj.art-8baf75dcdb2a44d88b0371d4c951d19b2022-12-22T01:34:24ZengWileyAnimal Models and Experimental Medicine2576-20952022-06-015321722610.1002/ame2.12253Role of miR‐21‐5p/FilGAP axis in estradiol alleviating the progression of monocrotaline‐induced pulmonary hypertensionXiaoyi Hu0Qian Wang1Hui Zhao2Wenhui Wu3Qinhua Zhao4Rong Jiang5Jinming Liu6Lan Wang7Ping Yuan8Department of Cardio‐Pulmonary Circulation Shanghai Pulmonary Hospital School of Medicine Tongji University Shanghai 200433 ChinaDepartment of Cardio‐Pulmonary Circulation Shanghai Pulmonary Hospital School of Medicine Tongji University Shanghai 200433 ChinaDepartment of Cardio‐Pulmonary Circulation Shanghai Pulmonary Hospital School of Medicine Tongji University Shanghai 200433 ChinaDepartment of Cardio‐Pulmonary Circulation Shanghai Pulmonary Hospital School of Medicine Tongji University Shanghai 200433 ChinaDepartment of Cardio‐Pulmonary Circulation Shanghai Pulmonary Hospital School of Medicine Tongji University Shanghai 200433 ChinaDepartment of Cardio‐Pulmonary Circulation Shanghai Pulmonary Hospital School of Medicine Tongji University Shanghai 200433 ChinaDepartment of Cardio‐Pulmonary Circulation Shanghai Pulmonary Hospital School of Medicine Tongji University Shanghai 200433 ChinaDepartment of Cardio‐Pulmonary Circulation Shanghai Pulmonary Hospital School of Medicine Tongji University Shanghai 200433 ChinaDepartment of Cardio‐Pulmonary Circulation Shanghai Pulmonary Hospital School of Medicine Tongji University Shanghai 200433 ChinaAbstract Background Aberrant expression of microRNAs (miRNAs) has been associated with the pathogenesis of pulmonary hypertension (PH). It is, however, not clear whether miRNAs are involved in estrogen rescue of PH. Methods Fresh plasma samples were prepared from 12 idiopathic pulmonary arterial hypertension (IPAH) patients and 12 healthy controls undergoing right heart catheterization in Shanghai Pulmonary Hospital. From each sample, 5 μg of total RNA was tagged and hybridized on microRNA microarray chips. Monocrotaline‐induced PH (MCT‐PH) male rats were treated with 17β‐estradiol (E2) or vehicle. Subgroups were cotreated with estrogen receptor (ER) antagonist or with antagonist of miRNA. Results Many circulating miRNAs, including miR‐21‐5p and miR‐574‐5p, were markedly expressed in patients and of interest in predicting mean pulmonary arterial pressure elevation in patients. The expression of miR‐21‐5p in the lungs was significantly upregulated in MCT‐PH rats compared with the controls. However, miR‐574‐5p showed no difference in the lungs of MCT‐PH rats and controls. miR‐21‐5p was selected for further analysis in rats as E2 strongly regulated it. E2 decreased miR‐21‐5p expression in the lungs of MCT‐PH rats by ERβ. E2 reversed miR‐21‐5p target gene FilGAP downregulation in the lungs of MCT‐PH rats. The abnormal expression of RhoA, ROCK2, Rac1 and c‐Jun in the lungs of MCT‐PH rats was inhibited by E2 and miR‐21‐5p antagonist. Conclusions miR‐21‐5p level was remarkably associated with PH severity in patients. Moreover, the miR‐21‐5p/FilGAP signaling pathway modulated the protective effect of E2 on MCT‐PH through ERβ.https://doi.org/10.1002/ame2.1225317β‐estradiolestrogen receptor antagonistFilGAPmiR‐21‐5ppulmonary hypertension |
| spellingShingle | Xiaoyi Hu Qian Wang Hui Zhao Wenhui Wu Qinhua Zhao Rong Jiang Jinming Liu Lan Wang Ping Yuan Role of miR‐21‐5p/FilGAP axis in estradiol alleviating the progression of monocrotaline‐induced pulmonary hypertension Animal Models and Experimental Medicine 17β‐estradiol estrogen receptor antagonist FilGAP miR‐21‐5p pulmonary hypertension |
| title | Role of miR‐21‐5p/FilGAP axis in estradiol alleviating the progression of monocrotaline‐induced pulmonary hypertension |
| title_full | Role of miR‐21‐5p/FilGAP axis in estradiol alleviating the progression of monocrotaline‐induced pulmonary hypertension |
| title_fullStr | Role of miR‐21‐5p/FilGAP axis in estradiol alleviating the progression of monocrotaline‐induced pulmonary hypertension |
| title_full_unstemmed | Role of miR‐21‐5p/FilGAP axis in estradiol alleviating the progression of monocrotaline‐induced pulmonary hypertension |
| title_short | Role of miR‐21‐5p/FilGAP axis in estradiol alleviating the progression of monocrotaline‐induced pulmonary hypertension |
| title_sort | role of mir 21 5p filgap axis in estradiol alleviating the progression of monocrotaline induced pulmonary hypertension |
| topic | 17β‐estradiol estrogen receptor antagonist FilGAP miR‐21‐5p pulmonary hypertension |
| url | https://doi.org/10.1002/ame2.12253 |
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