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Dysregulation of CREB binding protein triggers thrombin-induced proliferation of vascular smooth muscle cells

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Abstract

Thrombin is a potent mitogen for vascular smooth muscle cells (VSMCs). CBP has been regarded as a potential therapeutic target on the basis of its ability to affect cell growth. Therefore we hypothesized that CBP mediates thrombin-induced proliferation of VSMCs. We constructed recombinant adenoviral vector that expresses four short hairpin RNA (shRNA) targeting rat CBP mRNA (CBP-shRNA/Ad). VSMCs were infected with CBP-shRNA/Ad and treated with thrombin. CBP level were analyzed by quantitative real-time PCR and Western blot. To evaluate VSMC proliferation, the cell cycle and DNA synthesis were analyzed by flow cytometry and 3H-thymidine incorporation, respectively. CBP-shRNA/Ad infection inhibited thrombin-induced CBP expression in a dose-dependent manner concomitant with a decrease in the percentage of cells in the S phase and in DNA synthesis. These findings suggest that CBP plays a pivotal role in the S phase progression of VSMCs.

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Acknowledgment

This project was supported by National Science Foundation of China NSDC No. 30770849.

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Authors and Affiliations

  1. Department of Cardiology, Renmin Hospital, Wuhan University, Wuhan, 430060, China

    Jing Chen, Hong Jiang, Lin Xu, Li-Hua Zhu, Lang Wang, Hua-Zhi Wen & Xiao-Rong Hu

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  1. Jing Chen
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  2. Hong Jiang
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  3. Lin Xu
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Correspondence to Hong Jiang.

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Chen, J., Jiang, H., Xu, L. et al. Dysregulation of CREB binding protein triggers thrombin-induced proliferation of vascular smooth muscle cells. Mol Cell Biochem 315, 123–130 (2008). https://doi.org/10.1007/s11010-008-9795-4

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  • DOI: https://doi.org/10.1007/s11010-008-9795-4

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