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01-03-2012

Toxicological Insight from AP-1 Silencing Study on Proliferation, Migration, and Dedifferentiation of Rat Vascular Smooth Muscle Cell

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

Published in: Cardiovascular Toxicology | Issue 1/2012

Abstract

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.

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Title: Toxicological Insight from AP-1 Silencing Study on Proliferation, Migration, and Dedifferentiation of Rat Vascular Smooth Muscle Cell
Authors: Hong-Wei Zhang
Tao Zhang
Bao-Zhong Shen
Ming Liu
Jia-Ren Liu
Publication date: 01-03-2012
Publisher: Humana Press Inc
Published in: Cardiovascular Toxicology / Issue 1/2012
Print ISSN: 1530-7905
Electronic ISSN: 1559-0259
DOI: https://doi.org/10.1007/s12012-011-9135-x

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Toxicological Insight from AP-1 Silencing Study on Proliferation, Migration, and Dedifferentiation of Rat Vascular Smooth Muscle Cell

Abstract

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Abstract

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