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Galpha12 Protects Vascular Endothelial Cells from Serum Withdrawal-Induced Apoptosis through Regulation of miR-155

 Hyeon Jeong Lee  ;  Eun Jig Lee  ;  Mi Ran Seo 
 YONSEI MEDICAL JOURNAL, Vol.57(1) : 247-253, 2016 
Journal Title
Issue Date
Apoptosis* ; Atherosclerosis/blood* ; Atherosclerosis/genetics ; Atherosclerosis/immunology ; Cell Proliferation ; Endothelial Cells/metabolism* ; GTP-Binding Protein alpha Subunits, G12-G13/genetics* ; Gene Expression Profiling ; Gene Expression Regulation ; Human Umbilical Vein Endothelial Cells/cytology ; Humans ; MicroRNAs/metabolism* ; Protective Agents ; RNA, Small Interfering* ; Real-Time Polymerase Chain Reaction ; Transfection*
Gα12 protein ; apoptosis ; endothelial cells ; microRNAs
PURPOSE: 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. MATERIALS AND 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. CONCLUSION: 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.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Lee, Eun Jig(이은직) ORCID logo https://orcid.org/0000-0002-9876-8370
Lee, Hyeon Jeong(이현정) ORCID logo https://orcid.org/0000-0003-0635-5454
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