tMfn 2 gene induces apoptosis of vascular smooth muscle cells
10.3969/j.issn.1673-8225.2009.41.040
- VernacularTitle:tMfn2基因诱导血管平滑肌细胞的凋亡
- Author:
Li ZHAO
;
Wei ZHOU
;
Guanghui CHEN
;
Xiaomei GUO
- Publication Type:Journal Article
- From:
Chinese Journal of Tissue Engineering Research
2009;13(41):8187-8191
- CountryChina
- Language:Chinese
-
Abstract:
BACKGROUND: Mitofusin2 (Mfn2) profoundly inhibits proliferation and induces apoptosis of vascular smooth muscle cells (VSMCs) through phosphatidylinositol 3 kinase/protein kinase B. Notably, tMfn2, with the transmembrane domain deleted, has a 41%-reduced molecular weight, which possibly exhibits a stronger effect on inducing apoptosis.OBJECTIVE: To investigate the effect of rat tMfn2 gene, with the transmembrane domain deleted, on promoting the apoptosis of VSMCs, and to determine related signal pathway.DESIGN, SETTING AND TIME: A controlled observational study at a gene level was performed in the central laboratory, Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology between January and October in 2008.MATERIALS: Rat VSMCs and the recombinant adenovirus containing LacZ, Mfn2 or tMfn2 was offered by Professor Chen as a gift.METHODS: The rat VSMCs cultured at 3-10 passages were divided into 4 groups. ①Blank control group: No interventions. ② VSMCs were infected by adenovirus-mediated LacZ, Mfn2, and tMfn2, respectively.MAIN OUTCOME MEASURES: ①Expressions of Mfn2 and tMfn2 following the VSMCs were infected with recombinant adenovirus for 24 hours. ②The apoptosis of VSMCs was determined with flow cytometry and enzyme linked immunosorbent assay at 24, 48 and 72 hours following infection. ③Western blot was used to analyze the expression of phosphorylated AKT following the VSMCs were infected with recombinant adenovirus for 24 hours.RESULTS: ①Both Mfn2 and tMfn2 were expressed in the VSMCs. ②The tMfn2 was superior to Mfn2 in promoting the apoptosis of VSMCs in a time-dependent manner (P<0.01). ③The protein expression of phosphorylated AKT remarkably decreased two groups, especially significant in tMfn2-infected group (P<0,01).CONCLUSION: The tMfn2 can induce the apoptosis of VSMCs more effectively via the inhibition of phosphorylated AKT signaling pathway.
