Role of miR-21-5p/FilGAP axis in estradiol alleviating the progression of monocrotaline-induced pulmonary hypertension  

作　　者：Xiaoyi Hu Qian Wang Hui Zhao Wenhui Wu Qinhua Zhao Rong Jiang Jinming Liu Lan Wang Ping Yuan 

机构地区：[1]Department of Cardio-Pulmonary Circulation,Shanghai Pulmonary Hospital,School of Medicine,Tongji University,Shanghai 200433,China [2]Institute of Bismuth Science,University of Shanghai for Science and Technology,Shanghai,China

出　　处：《Animal Models and Experimental Medicine》2022年第3期217-226,共10页动物模型与实验医学（英文）

基　　金：National Natural Science Foundation of China,Grant/Award Number:8 1870042;Natural Science Foundation of Shanghai,Grant/Award Number:21ZR1453800。

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,5μg of total RNA was tagged and hybridized on microRNA microarray chips.Monocrotaline-induced 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.

关 键 词：17Β-ESTRADIOL estrogen receptor antagonist FilGAP miR-21-5p pulmonary hypertension 

分 类 号：R544.1[医药卫生—心血管疾病]