DOI: 10.1002/ame2.12253
Role of miR - 21- 5p/ FilGAP axis in estradiol alleviating the progression of monocrotaline- induced pulmonary hypertension
Xiaoyi Hu1
Qian Wang2
Hui Zhao2
Wenhui Wu1
Qinhua Zhao1
Rong Jiang1
Jinming Liu1
Lan Wang1
Ping Yuan1
1.Department of Cardio-Pulmonary Circulation,Shanghai Pulmonary Hospital,School of Medicine,Tongji University, Shanghai 200433,China2.Department of Cardio-Pulmonary Circulation,Shanghai Pulmonary Hospital,School of Medicine,Tongji University, Shanghai 200433,China;Institute of Bismuth Science,University of Shanghai for Science and Technology,Shanghai,China
摘要：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 cath-eterization in Shanghai Pulmonary Hospital. From each sample, 5 μg of total RNA was tagged and hybridized on microRNA microarray chips. Monocrotaline-i nduced PH (MCT- PH) male rats were treated with 17β- estradiol (E 2 ) 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 mark-edly expressed in patients and of interest in predicting mean pulmonary arterial pres-sure 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 se-lected for further analysis in rats as E 2 strongly regulated it. E 2 decreased miR- 21- 5p expression in the lungs of MCT- PH rats by ERβ. E 2 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 E 2 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 E 2 on MCT- PH through ERβ.
机标关键词：hypertensionaxisrolealleviatingestradiolfilgapinducedmonocrotaline-
论文发表日期：2022-06-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：10( 217-226 )
英文信息