Rab1 GTPase regulates phenotypic modulation of pulmonary artery smooth muscle cells by mediating the transport of angiotensin II type 1 receptor under hypoxia.
Rab1 GTPase regulates phenotypic modulation of pulmonary artery smooth muscle cells by mediating the transport of angiotensin II type 1 receptor under hypoxia.
复制标题
DOI：
10.1016/j.biocel.2010.11.010
复制
发表时间：
2011-03
影响因子：
4
通讯作者：
Wang, Guansong
中科院分区：
文献类型：
--
作者：
Yin, Hongjin;Li, Qi;Qian, Guisheng;Wang, Yaoli;Li, Yuncheng;Wu, Guangyu;Wang, Guansong
关键词：
以往的研究表明Rab 1参与血管紧张素II（AngII）1型受体（AT 1 R）向内皮细胞和心肌细胞表面的输出。本研究的目的是评估是否修改Rab 1介导的内质网（ER）的高尔基体运输改变细胞表面的表达和功能的内源性AT 1 R和AT 1 R介导的表型调制在原代培养的肺动脉平滑肌细胞（PASMCs）。野生型Rab 1（Rab 1 WT）的慢病毒表达显著增加了内源性AT 1 R的细胞表面表达。而Rab 1 siRNA则相反，可减弱低氧对大鼠肺动脉平滑肌细胞（RPASMCs）表型标志物α-平滑肌肌动蛋白（α-SMA）和波形蛋白（Vim）表达的下调作用。AT 1 R的亚细胞定位分析表明，Rab 1调节AT 1 R从内质网到高尔基体的运输。与它们对AT 1 R输出的作用一致，Rab 1在缺氧期间修饰AT 1 R介导的细胞生长和信号转导转录激活因子3（STAT 3）的磷酸化。我们发现，缺氧促进Rab 1的表达，并与RPASMCs中PASMC表型标记物的表达抑制密切相关。这些数据有力地表明，Rab 1通过操纵AT 1 R从ER到高尔基体的运输来调节PASMCs的功能，并提供了第一个证据，表明ER到高尔基体的运输是控制RPASMCs生长的调节步骤。
Previous studies have demonstrated that Rab1 is involved in the export of angiotensin II (Ang II) type 1 receptor (AT1R) to the cell surface in endothelial cells and cardiomyocytes. The aim of this study was to evaluate whether the modification of Rab1-mediated endoplasmic reticulum (ER) to the Golgi body transport alters the cell surface expression and function of endogenous AT1R and AT1R-mediated phenotypic modulation in primary cultures of pulmonary artery smooth muscle cells (PASMCs). Lentiviral expression of wild-type Rab1 (Rab1WT) significantly increased cell surface expression of endogenous AT1R. However, Rab1 siRNA had the opposite effect, and attenuated downregulation of the expression of PASMCs phenotype markers, α smooth muscle actin (α-SMA) and vimentin (VIM) in rat pulmonary artery smooth muscle cells (RPASMCs) during hypoxia. Analysis of the subcellular localization of AT1R revealed that Rab1 regulated AT1R transport from the ER to the Golgi in PASMCs. Consistent with their effects on AT1R export, Rab1 modified the AT1R-mediated cell growth and the phosphorylation of signal transducing activator of transcription 3 (STAT3) during hypoxia. We found that hypoxia promoted Rab1 expression and strongly correlated with the repressed expression of PASMC phenotype markers in RPASMCs. These data strongly indicate that Rab1 modulates PASMCs function by manipulating AT1R traffic from the ER to the Golgi and provide the first evidence implicating ER-to-Golgi transport as a regulatory step for the control of RPASMCs growth.
登录
查看更多内容
影响因子：
5.6
作者：
Pereira-Leal, JB;Seabra, MC
通讯作者：
Seabra, MC
影响因子：
3.3
作者：
Fletcher, EC;Orolinova, N;Bader, M
通讯作者：
Bader, M
影响因子：
4.8
作者：
Duvernay, MT;Zhou, FG;Wu, GY
通讯作者：
Wu, GY
影响因子：
3.3
作者：
Saraste, Jaakko;Goud, Bruno
通讯作者：
Goud, Bruno
DOI：
10.1016/j.biocel.2007.08.008
发表时间：
2008-01-01
影响因子：
4
作者：
Wang, Guansong;Qian, Pin;Wu, Guangyu
通讯作者：
Wu, Guangyu