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Article

A novel PI3K inhibitor alleviates fibrotic responses in fibroblasts derived from Peyronie's plaques

  • Authors:
    • Kyung Hee Jung
    • Ye-Lim Ryu
    • Hee-Seung Lee
    • Hyunseung Lee
    • Mi Kwon Son
    • Hong Hua Yan
    • Sang-Won Hong
    • Ji-Kan Ryu
    • Sungwoo Hong
    • Jun‑Kyu Suh
    • Soon-Sun Hong
  • View Affiliations / Copyright

    Affiliations: Department of Biomedical Sciences, College of Medicine, Inha University, Incheon 400-712, Republic of Korea, National Research Center for Sexual Medicine, College of Medicine, Inha University, Incheon 400-712, Republic of Korea, Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea
  • Pages: 2001-2008
    |
    Published online on: April 16, 2013
       https://doi.org/10.3892/ijo.2013.1905
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Abstract

Peyronie's disease (PD) is fibrosis localized in the tunica albuginea that is characterized by penile deformity and curvature. The pathogenesis of this disease remains unclear even though transforming growth factor‑β (TGF-β)/smad signalling has been reported to be associated with PD. Recent studies have shown that phosphoinositide 3-kinase (PI3K)/Akt signalling regulates fibrotic responses including collagen synthesis and cell proliferation. Thus, we synthesized HS-173, a novel PI3K inhibitor, and determined whether this compound has anti-fibrotic effects on PD-derived primary fibroblasts. In this study, we found that HS-173 inhibited the growth of fibroblasts in a dose-dependent manner and induced apoptosis. In addition, HS-173 reduced the expression of α-smooth muscle actin (α-SMA), vimentin, PAI-1, fibronectin, collagen type I, collagen IV and TGF-β-activated smad2/3 in PD-derived primary fibroblasts. HS-173 blocked the PI3K/Akt signalling pathway by decreasing the activation of Akt, mTOR and P70S6K. Our results showed that HS-173 suppressed fibrotic responses such as cell proliferation and collagen synthesis by blocking PI3K/Akt signalling in PD-derived primary fibroblasts. Our findings provide molecular insights into the potential therapeutic action of HS-173 through targeting the PI3K/Akt pathway in PD-derived fibroblasts and demonstrated that HS-173 could be used as a pharmacological agent for treating other fibrotic diseases.
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Copy and paste a formatted citation
Spandidos Publications style
Jung KH, Ryu Y, Lee H, Lee H, Son MK, Yan HH, Hong S, Ryu J, Hong S, Suh JK, Suh JK, et al: A novel PI3K inhibitor alleviates fibrotic responses in fibroblasts derived from Peyronie's plaques. Int J Oncol 42: 2001-2008, 2013.
APA
Jung, K.H., Ryu, Y., Lee, H., Lee, H., Son, M.K., Yan, H.H. ... Hong, S. (2013). A novel PI3K inhibitor alleviates fibrotic responses in fibroblasts derived from Peyronie's plaques. International Journal of Oncology, 42, 2001-2008. https://doi.org/10.3892/ijo.2013.1905
MLA
Jung, K. H., Ryu, Y., Lee, H., Lee, H., Son, M. K., Yan, H. H., Hong, S., Ryu, J., Hong, S., Suh, J., Hong, S."A novel PI3K inhibitor alleviates fibrotic responses in fibroblasts derived from Peyronie's plaques". International Journal of Oncology 42.6 (2013): 2001-2008.
Chicago
Jung, K. H., Ryu, Y., Lee, H., Lee, H., Son, M. K., Yan, H. H., Hong, S., Ryu, J., Hong, S., Suh, J., Hong, S."A novel PI3K inhibitor alleviates fibrotic responses in fibroblasts derived from Peyronie's plaques". International Journal of Oncology 42, no. 6 (2013): 2001-2008. https://doi.org/10.3892/ijo.2013.1905
Copy and paste a formatted citation
x
Spandidos Publications style
Jung KH, Ryu Y, Lee H, Lee H, Son MK, Yan HH, Hong S, Ryu J, Hong S, Suh JK, Suh JK, et al: A novel PI3K inhibitor alleviates fibrotic responses in fibroblasts derived from Peyronie's plaques. Int J Oncol 42: 2001-2008, 2013.
APA
Jung, K.H., Ryu, Y., Lee, H., Lee, H., Son, M.K., Yan, H.H. ... Hong, S. (2013). A novel PI3K inhibitor alleviates fibrotic responses in fibroblasts derived from Peyronie's plaques. International Journal of Oncology, 42, 2001-2008. https://doi.org/10.3892/ijo.2013.1905
MLA
Jung, K. H., Ryu, Y., Lee, H., Lee, H., Son, M. K., Yan, H. H., Hong, S., Ryu, J., Hong, S., Suh, J., Hong, S."A novel PI3K inhibitor alleviates fibrotic responses in fibroblasts derived from Peyronie's plaques". International Journal of Oncology 42.6 (2013): 2001-2008.
Chicago
Jung, K. H., Ryu, Y., Lee, H., Lee, H., Son, M. K., Yan, H. H., Hong, S., Ryu, J., Hong, S., Suh, J., Hong, S."A novel PI3K inhibitor alleviates fibrotic responses in fibroblasts derived from Peyronie's plaques". International Journal of Oncology 42, no. 6 (2013): 2001-2008. https://doi.org/10.3892/ijo.2013.1905
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