Rab1 GTPase regulates phenotypic modulation of pulmonary artery smooth muscle cells by mediating the transport of angiotensin II type 1 receptor under hypoxia

Hongjin Yin, Qi Li, Guisheng Qian, Yaoli Wang, Yuncheng Li, Guangyu Wu, Guansong Wang

Research output: Contribution to journalArticle

18 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)401-408
Number of pages8
JournalInternational Journal of Biochemistry and Cell Biology
Volume43
Issue number3
DOIs
StatePublished - Mar 1 2011

Keywords

  • Angiotensin II type 1 receptor
  • Hypoxia
  • Phenotypic modulation
  • Pulmonary artery smooth muscle cells
  • Rab1 GTPase

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Fingerprint Dive into the research topics of 'Rab1 GTPase regulates phenotypic modulation of pulmonary artery smooth muscle cells by mediating the transport of angiotensin II type 1 receptor under hypoxia'. Together they form a unique fingerprint.

  • Cite this