title: Galpha12 Protects Vascular Endothelial Cells from Serum Withdrawal-Induced Apoptosis through Regulation of miR-155.
abstract: OBJECTIVE
  Apoptosis of vascular endothelial cells is a type of endothelial damage that is associated with the pathogenesis of cardiovascular diseases such as atherosclerosis. Heterotrimeric GTP-binding proteins (G proteins), including the alpha 12 subunit of G protein (Gα12), have been found to modulate cellular proliferation, differentiation, and apoptosis of numerous cell types. However, the role of Gα12 in the regulation of apoptosis of vascular cells has not been elucidated. We investigated the role of Gα12 in serum withdrawal-induced apoptosis of human umbilical vein endothelial cells (HUVECs) and its underlying mechanisms.
  
  
  METHODS
  HUVECs were transfected with Gα12 small-interfering RNA (siRNA) to knockdown the endogenous Gα12 expression and were serum-deprived for 6 h to induce apoptosis. The apoptosis of HUVECs were assessed by Western blotting and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The expressions of microRNAs were analyzed by quantitative real-time PCR.
  
  
  RESULTS
  Knockdown of Gα12 with siRNA augmented the serum withdrawal-induced apoptosis of HUVECs and markedly repressed the expression of microRNA-155 (miR-155). Serum withdrawal-induced apoptosis of HUVECs was inhibited by the overexpression of miR-155 and increased significantly due to the inhibition of miR-155. Notably, the elevation of miR-155 expression prevented increased apoptosis of Gα12-deficient HUVECs.
  
  
  CONCLUSIONS
  From these results, we conclude that Gα12 protects HUVECs from serum withdrawal-induced apoptosis by retaining miR-155 expression. This suggests that Gα12 might play a protective role in vascular endothelial cells by regulating the expression of microRNAs.
authors.affiliation: Department of Endocrinology, Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hyeon Jeong
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Endocrinology, Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea. ejlee423@yuhs.ac.
authors.forename: Eun Jig
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: Severance Hospital Integrative Research Institute for Cerebral & Cardiovascular Disease, Yonsei University College of Medicine, Seoul, Korea. seo99@yuhs.ac.
authors.forename: MiRan
authors.initials: M
authors.lastname: Seo
mesh_terms: D017209:Apoptosis; D050197:Atherosclerosis / Q000097:blood* / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000378:metabolism*; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000235:genetics*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D020011:Protective Agents; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection
chemical_list: D035683:MicroRNAs; D020011:Protective Agents; D034741:RNA, Small Interfering; D044365:GTP-Binding Protein alpha Subunits, G12-G13
keywords: Gα12 protein; apoptosis; endothelial cells; microRNAs