Toxicological insight from AP-1 silencing study on proliferation, migration, and dedifferentiation of rat vascular smooth muscle cell.

Hong-Wei Zhang, Tao Zhang, Bao-Zhong Shen, Ming Liu, Jia-Ren Liu

Treatment Center of Oncology, The Fourth Affiliated Hospital of Harbin Medical University, NanGang District, Harbin, The People's Republic of China.

Cardiovascular toxicology 2012 Mar

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There has an effective way to prevent intimal hyperplasia on vascular smooth muscle cell (VSMC) proliferation in grafted veins. The activator protein-1 (AP-1) transcription factor plays an important role in cardiovascular generation and angioplasty. Once activated, AP-1 binds its specific DNA sequence to promote the proliferation of VSMC, differentiation, and migration. The objectives of this study were to determine toxicological effects of AP-1 silencing study on proliferation, migration, and dedifferentiation of rat vascular smooth muscle cell. To suppress the expression of AP-1 gene, AP-1 siRNA was used to interfere post-transcription in rat primary VSMCs. To observe the expression of SM α-actin and downstream genes of AP-1, the activity of cell matrix metal proteinases and the migration ability of VSMC was examined by a modified Boyden chamber assay. Effects of AP-1 siRNA on proliferation and differentiation in rat VSMCs were evaluated by cell cycle analysis, DNA synthesis, MTT-test, and immunofluorescence. The results showed that the level of SM α-actin protein expression was increased. AP-1 siRNA also significantly decreased the MTT extinction value, DNA synthesis, PCNA expression, and the cell migration velocity when compared to the control group. AP-1 siRNA also clearly arrested cell cycle of VSM at the G0/G1 phase. Zymographic and Western blotting analyses showed that AP-1 siRNA suppressed serum-induced MMP-2 expression. These data suggest that the AP-1 siRNA was able to effectively inhibit the proliferation, migration, and dedifferentiation of smooth muscle cells. Thus, AP-1 siRNA provides a novel method to prevent intimal hyperplasia in blood vessel angioplasty.

Citation

Hong-Wei Zhang, Tao Zhang, Bao-Zhong Shen, Ming Liu, Jia-Ren Liu. Toxicological insight from AP-1 silencing study on proliferation, migration, and dedifferentiation of rat vascular smooth muscle cell. Cardiovascular toxicology. 2012 Mar;12(1):25-38