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International Journal of Molecular Medicine
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Article

Inhibition of farnesyl pyrophosphate synthase attenuates angiotensin II-induced fibrotic responses in vascular smooth muscle cells

  • Authors:
    • Chang-Qing Du
    • Xiao-Wei Liu
    • Guang-Zhong Zeng
    • Hong-Feng Jin
    • Li-Jiang Tang
  • View Affiliations / Copyright

    Affiliations: Department of Cardiology, Zhejiang Hospital, Hangzhou, Zhejiang 310013, P.R. China
  • Pages: 1767-1772
    |
    Published online on: April 2, 2015
       https://doi.org/10.3892/ijmm.2015.2166
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Abstract

Through the regulation of the RhoA/Rho kinase (ROCK) pathway, angiotensin II (Ang II)-induced fibrotic responses contribute to vascular remodeling. Farnesyl pyrophosphate synthase (FPPS) plays an important role in cardiovascular remodeling through the modulation of the above-mentioned pathway. However, the role of FPPS in Ang II-induced fibrotic responses and the related molecular mechanisms have not yet been elucidated. In the present study, vascular smooth muscle cells (VSMCs) from Sprague-Dawley (SD) rats were stimulated with Ang II. Cell proliferation was measusred usin the cell counting kit-8 (CCK-8). The levels of connective tissue growth factor (CTGF), FPPS, and those of phosphorylated and total extracellular signal-regulated kinase (ERK)1/2, p38 and c-Jun N-terminal kinase (JNK) were determined by western blot analysis. RhoA activity was determined using a pull-down assay. The results revealed that stimulation with Ang II enhanced cell proliferation, and increased the protein expression levels of FPPS and CTGF in the VSMCs. The inhibition of FPPS with ibandronate sodium attenuated the Ang II-induced increase in cell proliferation, CTGF expresison and RhoA activity; these effects were partially reversed by treatment with geranylgeraniol and were mimicked by GGTI-286. Furthermore, both SB203580 (a specific inhibitor of p38) and SP600125 (JNK1, JNK2 and JNK3 inhibitor) diminished the Ang II-induced production of CTGF; however, the inhibition of FPPS reduced the Ang II-induced activation of p38 mitogen-activated protein kinase (MAPK) and JNK. In conclusion, our data indicate that FPPS may play an important role in Ang II-induced fibrotic responses in VSMCs, and the underlying mechanisms at least partly involve the modulation of RhoA activity, and the p38 and JNK pathways.
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Copy and paste a formatted citation
Spandidos Publications style
Du C, Liu X, Zeng G, Jin H and Tang L: Inhibition of farnesyl pyrophosphate synthase attenuates angiotensin II-induced fibrotic responses in vascular smooth muscle cells. Int J Mol Med 35: 1767-1772, 2015.
APA
Du, C., Liu, X., Zeng, G., Jin, H., & Tang, L. (2015). Inhibition of farnesyl pyrophosphate synthase attenuates angiotensin II-induced fibrotic responses in vascular smooth muscle cells. International Journal of Molecular Medicine, 35, 1767-1772. https://doi.org/10.3892/ijmm.2015.2166
MLA
Du, C., Liu, X., Zeng, G., Jin, H., Tang, L."Inhibition of farnesyl pyrophosphate synthase attenuates angiotensin II-induced fibrotic responses in vascular smooth muscle cells". International Journal of Molecular Medicine 35.6 (2015): 1767-1772.
Chicago
Du, C., Liu, X., Zeng, G., Jin, H., Tang, L."Inhibition of farnesyl pyrophosphate synthase attenuates angiotensin II-induced fibrotic responses in vascular smooth muscle cells". International Journal of Molecular Medicine 35, no. 6 (2015): 1767-1772. https://doi.org/10.3892/ijmm.2015.2166
Copy and paste a formatted citation
x
Spandidos Publications style
Du C, Liu X, Zeng G, Jin H and Tang L: Inhibition of farnesyl pyrophosphate synthase attenuates angiotensin II-induced fibrotic responses in vascular smooth muscle cells. Int J Mol Med 35: 1767-1772, 2015.
APA
Du, C., Liu, X., Zeng, G., Jin, H., & Tang, L. (2015). Inhibition of farnesyl pyrophosphate synthase attenuates angiotensin II-induced fibrotic responses in vascular smooth muscle cells. International Journal of Molecular Medicine, 35, 1767-1772. https://doi.org/10.3892/ijmm.2015.2166
MLA
Du, C., Liu, X., Zeng, G., Jin, H., Tang, L."Inhibition of farnesyl pyrophosphate synthase attenuates angiotensin II-induced fibrotic responses in vascular smooth muscle cells". International Journal of Molecular Medicine 35.6 (2015): 1767-1772.
Chicago
Du, C., Liu, X., Zeng, G., Jin, H., Tang, L."Inhibition of farnesyl pyrophosphate synthase attenuates angiotensin II-induced fibrotic responses in vascular smooth muscle cells". International Journal of Molecular Medicine 35, no. 6 (2015): 1767-1772. https://doi.org/10.3892/ijmm.2015.2166
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