MEIS1 regulated proliferation and migration of pulmonary artery smooth muscle cells in hypoxia-induced pulmonary hypertension
MEIS1 regulated proliferation and migration of pulmonary artery smooth muscle cells in hypoxia-induced pulmonary hypertension
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MEIS1在缺氧诱导的肺动脉高压中调节肺动脉平滑肌细胞的增殖和迁移
DOI：
10.1016/j.lfs.2020.117822
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发表时间：
2020
期刊：
影响因子：
6.1
通讯作者：
Chang-Ping Hu
中科院分区：
文献类型：
--
作者：
Mao-Zhong Yao;Xiao-Yue Ge;Ting Liu;Ning Huang;Hong Liu;Yu Chen;Zheng Zhang;Chang-Ping Hu
目的肺动脉平滑肌细胞（PASMCs）的增殖和迁移被认为是肺动脉高压（PH）肺动脉重构的主要因素。髓样嗜亲性病毒整合位点1（MEIS 1）被定位为心肌细胞周期负调控因子，并调控多种癌细胞的增殖。方法将SD道利大鼠暴露于10%O2环境中4周，诱导肺动脉高压（PH）;将原代大鼠PASMCs在3%O2环境中培养48 h，诱导PASMCs增殖和迁移。采用免疫组化、免疫荧光、逆转录PCR和Western blot等方法检测靶基因mRNA和蛋白的表达。结果低氧可下调肺动脉和PASMCs中MEIS 1的表达（包括mRNA和蛋白）。MEIS 1过表达可抑制缺氧条件下PASMCs的增殖和迁移。在低氧等常氧条件下，MEIS 1基因的敲除可诱导PASMCs增殖和迁移。MEIS 1通过胃L14/MEIS 1/p21信号通路介导低氧诱导PASMCs增殖和迁移。
AimProliferation and migration of pulmonary artery smooth muscle cells (PASMCs) are regarded as the primary factors resulting in pulmonary arterial remodeling in pulmonary hypertension (PH). Myeloid ecotropic viral integration site 1 (MEIS1) has been positioned as a negative cardiomyocyte cell cycle regulator and regulates proliferation of multiple kinds of cancer cells. Whether MESI1 is involved in the proliferation and migration of PASMCs deserves to be identified.Main methodsSprague Dawley rats were exposed to hypoxia condition (10% O2) for 4 weeks to induce PH and primary rat PASMCs were cultured in hypoxia condition (3% O2) for 48 h to induce proliferation and migration. Immunohistochemistry, immunofluorescence, reverse transcription PCR and Western blot analysis were performed to detect the expressions of target mRNAs and proteins. EDU, CCK8 and wound healing assays were conducted to measure the proliferation and migration of PASMCs.Key findingsHypoxia down-regulated the expression of MEIS1 (both mRNA and protein) in pulmonary arteries and PASMCs. Over-expression of MEIS1 inhibited the proliferation and migration of PASMCs afforded by hypoxia. In contrast, knockdown of MEIS1 under normoxia condition like hypoxia induced the proliferation and migration of PASMCs. MEIS1 mediated hypoxia-induced the proliferation and migration of PASMCs via METTL14/MEIS1/p21 signaling.SignificanceThe present study revealed that MEIS1 regulated the proliferation and migration of PASMCs during hypoxia-induced PH. Thus, MEIS1 may be a potential target for PH therapy.