当前位置: X-MOL 学术J. Cardiovasc. Pharmacol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
ZIP12 Contributes to Hypoxic Pulmonary Hypertension by Driving Phenotypic Switching of Pulmonary Artery Smooth Muscle Cells
Journal of Cardiovascular Pharmacology ( IF 3 ) Pub Date : 2022-02-01 , DOI: 10.1097/fjc.0000000000001156
Tiantian Zhu 1 , Xuan Wang 2 , Zijie Zheng 2 , Jinping Quan 1 , Yuhao Liu 1 , Yuting Wang 1 , Tianheng Liu 1 , Xu Liu 1 , Mi Wang 3 , Zheng Zhang 1, 2
Affiliation  

ZIP12, a plasmalemmal zinc transporter, reportedly promotes pulmonary vascular remodeling (PVR) by enhancing proliferation of pulmonary artery smooth muscle cells (PASMCs). However, the mechanisms of ZIP12 facilitating PASMCs proliferation remain incompletely appreciated. It has been acknowledged that proliferation-predisposing phenotypic switching of PASMCs can lead to PVR. Given that hypoxia triggers phenotypic switching of PASMCs and ZIP12 mediates PVR, this study aims to explore whether ZIP12-mediated phenotypic switching of PASMCs contributes to hypoxia-induced PVR. Rats were exposed to hypoxia (10% O2) for 3 weeks to induce PVR, and primary rat PASMCs were cultured under hypoxic condition (3% O2) for 48 hours to induce proliferation. Immunofluorescence, quantitative reverse transcription-polymerase chain reaction, and Western blot analysis were performed to detect the expression of target mRNAs and proteins. EdU incorporation and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay were conducted to measure the proliferation of PASMCs. Hypoxia upregulated ZIP12 expression (both mRNA and protein) in pulmonary arteries and PASMCs. Knockdown of ZIP12 inhibited phenotypic switching of PASMCs induced by hypoxia. We propose that HIF-1α/ZIP12/pERK pathway could represent a novel mechanism underlying hypoxia-induced phenotypic switching of PASMCs. Therapeutic targeting of ZIP12 could be exploited to treat PVR.



中文翻译:

ZIP12 通过驱动肺动脉平滑肌细胞的表型转换导致缺氧性肺动脉高压

据报道,ZIP12 是一种质膜锌转运蛋白,可通过增强肺动脉平滑肌细胞 (PASMC) 的增殖来促进肺血管重塑 (PVR)。然而,ZIP12 促进 PASMC 增殖的机制仍未完全了解。人们已经认识到,PASMCs 的增殖倾向表型转换可以导致 PVR。鉴于缺氧触发PASMCs的表型转换而ZIP12介导PVR,本研究旨在探讨ZIP12介导的PASMCs表型转换是否有助于缺氧诱导的PVR。大鼠缺氧(10%O 2 )3周诱导PVR,原代大鼠PASMC在缺氧(3%O 2 )条件下培养48小时诱导增殖。采用免疫荧光、定量逆转录聚合酶链反应和Western blot分析检测目标mRNA和蛋白的表达。进行 EdU 掺入和 3-(4,5-二甲基噻唑-2-基)-5-(3-羧甲氧基苯基)-2-(4-磺基苯基)-2H-四唑测定来测量 PASMC 的增殖。缺氧上调肺动脉和 PASMC 中的 ZIP12 表达(mRNA 和蛋白质)。ZIP12 的敲低抑制了缺氧诱导的 PASMCs表型转换。我们提出 HIF-1α/ZIP12/ p ERK 通路可能代表缺氧诱导PASMC 表型转换的一种新机制。ZIP12 的治疗靶向可用于治疗 PVR。

更新日期:2022-02-01
down
wechat
bug