Role and mechanism of myotubularin-related protein 7 in pulmonary hypertension in mice
- VernacularTitle:肌微管素相关微蛋白7在小鼠肺动脉高压中的作用及机制
- Author:
Jia WANG
1
;
Li ZHANG
;
Yao YANG
;
Xi YANG
;
Xiong-shan SUN
;
Yong-jian YANG
Author Information
- Publication Type:Journal Article
- Keywords: myotubularin-related proteins 7; ERK1/2; pulmonary vascular remodeling; pulmonary artery smooth muscle cells; pulmonary hypertension; right ventricular hypertrophy
- From: Chinese Pharmacological Bulletin 2025;41(1):57-65
- CountryChina
- Language:Chinese
- Abstract: Aim To investigate the role of myotubula-rin related protein 7(MTMR7)in the pathogenesis of pulmonary hypertension manifested by pulmonary vas-cular intimal thickening,right ventricular hypertrophy,progressive right heart failure and dysfunction.Meth-ods A total of 40 healthy male C57BL/6J mice and Mtmr7-transgenic(Mtmr7-Tg)mice were divided into the control group,Mtmr7-Tg group,monocrotaline(MCT)group and MCT+Mtmr7-Tg group.Pulmonary artery acceleration time(PAT)and pulmonary artery ejection time(PET)of the pulmonary artery were measured by ultrasound.When the free wall of the right ventricle was separated,the right heart hypertro-phy index(RVHI)was calculated.Pulmonary artery remodeling was observed by immunostaining.Mouse pulmonary artery smooth muscle cells(PASMCs)were cultured in hypoxic environment to induce the prolifer-ation and migration.Results MTMR7 was expressed in pulmonary vessels.Compared to the wild-type mice,Mtmr7-Tg mice showed increased PAT/PET ratio(P＜0.05),reduced RVHI(P＜0.01)after MCT stimu-lus.PASMCs were transfected with adenovirus encond-ing Mtmr7 gene,which inhibited proliferation and mi-gration of PASMCs.After restoring the activity of ERK1/2 by chemerin-9,the proliferation and migra-tion ability of PASMCs was elevated.Conclusions MTMR7 can counteract the growth and mobility of mouse PASMCs induced by hypoxia,thereby comba-ting pulmonary arterial hypertension via reducing ERK1/2 phosphorylation.
