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FTY720 induces cell cycle arrest and apoptosis of rat glomerular mesangial cells

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Abstract

The present study aimed to examine the effect of FTY720, a new immunosuppressive agent, on the proliferation and apoptosis of glomerular mesangial cells (GMC), and investigate the underlying mechanisms. Cultured rat GMC were treated by FTY720, and the cell viability, apoptosis and cell cycle progression were examined. Furthermore, cell cycle related gene expression profile was analyzed by cDNA microarray, and the protein expression of cell cycle related genes as well as Bax and Bcl-2 were examined by Western blot. The results showed that FTY720 inhibited GMC proliferation and induced apoptosis of GMC in a dose- and time-dependent manner, and induced G1 phase cell cycle arrest in GMC in a dose-dependent manner as well. cDNA microarray analysis revealed that FTY720 regulated the expression of cell cycle-related gene. Western blot analysis showed that FTY720 induced the downregulation of cyclin D1, cyclin E, CDK2, CDK4, Bcl-2 and E2F1 and the upregulation of Kip1/p27, Cip1/p21, Bax and Rb in GMC in a dose-dependent manner. These results demonstrated that FTY720 could inhibit the proliferation of GMC through inducing cell cycle arrest and apoptosis, probably via the regulation of the expression of cell cycle-related genes and Bax/Bcl-2.

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Acknowledgments

This work was supported in part by funds from the National Natural Science Foundation of China (No. 30472268, 81070557 to Jianhua Zhou), and a grant from Wuhan Science and Technology Bureau (No. 20096D638291 to Jingyu Jiang). The authors thank Dr. Mei Chen for her excellent work in the preparation of the manuscript.

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Authors and Affiliations

  1. Department of Pharmacy, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Shengli Street No. 26, Wuhan, 430014, China

    Jingyu Jiang, Yi Wang & Aiping Deng

  2. Department of Internal Medicine, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, China

    Xiaodong Huang

  3. Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Jianhua Zhou

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  1. Jingyu Jiang
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Correspondence to Jingyu Jiang or Jianhua Zhou.

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Jiang, J., Huang, X., Wang, Y. et al. FTY720 induces cell cycle arrest and apoptosis of rat glomerular mesangial cells. Mol Biol Rep 39, 8243–8250 (2012). https://doi.org/10.1007/s11033-012-1672-2

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  • DOI: https://doi.org/10.1007/s11033-012-1672-2

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