title: Rab1 GTPase regulates phenotypic modulation of pulmonary artery smooth muscle cells by mediating the transport of angiotensin II type 1 receptor under hypoxia.
abstract: 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.
authors.affiliation: Institute of Respiratory Diseases, the Second Affiliated Hospital of the Third Military Medical University, Chongqing 400037, PR China.
authors.forename: Hongjin
authors.initials: H
authors.lastname: Yin
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.forename: Guisheng
authors.initials: G
authors.lastname: Qian
authors.forename: Yaoli
authors.initials: Y
authors.lastname: Wang
authors.forename: Yuncheng
authors.initials: Y
authors.lastname: Li
authors.forename: Guangyu
authors.initials: G
authors.lastname: Wu
authors.forename: Guansong
authors.initials: G
authors.lastname: Wang
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015687:Cell Hypoxia; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D048430:Cell Shape; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000201:enzymology*; D010641:Phenotype; D010766:Phosphorylation; D021381:Protein Transport; D011651:Pulmonary Artery / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D020761:rab1 GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D044140:Receptor, Angiotensin, Type 1; D050796:STAT3 Transcription Factor; D020761:rab1 GTP-Binding Proteins