VEGF expression is augmented by hypoxia‑induced PGIS in human fibroblasts

  • Authors:
    • Jia Wang
    • Ryuji Ikeda
    • Xiao-Fang Che
    • Akio Ooyama
    • Masatatsu Yamamoto
    • Tatsuhiko Furukawa
    • Kazuhisa Hasui
    • Chun-Lei Zheng
    • Yusuke Tajitsu
    • Toshinori Oka
    • Sho Tabata
    • Yukihiko Nishizawa
    • Yoshito Eizuru
    • Shin-Ichi Akiyama
  • View Affiliations

  • Published online on: June 27, 2013     https://doi.org/10.3892/ijo.2013.1994
  • Pages: 746-754
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Abstract

Prostacyclin synthase (PGIS or PTGIS) is an enzyme that catalyses the conversion of prostaglandin H2 (PGH2) to prostaglandin I2 (PGI2). PGI2 promotes cancer growth by activating peroxisome proliferator-activated receptor δ (PPARδ), and increases the expression levels of the pro-angiogenic factor vascular endothelial growth factor (VEGF). We found that the expression of the PGIS gene was enhanced in WI-38, TIG-3-20 and HEL human lung fibroblast cells and two cancer cell lines (NB-1 and G361) under hypoxic conditions. The main localization of PGIS changed from the cytoplasm to the nucleus by hypoxia in WI-38 cells. The induced PGIS had an enzymatic activity since the intracellular level of 6-keto-prostaglandin, a useful marker of PGI2 biosynthesis in vivo, was increased with the increasing levels of PGIS. Expression of VEGF was increased in parallel with PGIS induction under hypoxic conditions. PGIS knockdown resulted in the decreased expression of VEGF mRNA. Since VEGF is a known PPARδ target gene, we examined the effects of siRNAs targeting PPARδ on the expression of VEGF under hypoxic conditions. Knockdown of PPARδ suppressed the expression of VEGF under hypoxic conditions in WI-38 cells. These findings suggest that PGIS is induced by hypoxia and regulates the expression of VEGF in fibroblasts. Fibroblasts in the hypoxic area of tumors may have an important role in tumor growth and angiogenesis.
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September 2013
Volume 43 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Wang J, Ikeda R, Che X, Ooyama A, Yamamoto M, Furukawa T, Hasui K, Zheng C, Tajitsu Y, Oka T, Oka T, et al: VEGF expression is augmented by hypoxia‑induced PGIS in human fibroblasts. Int J Oncol 43: 746-754, 2013.
APA
Wang, J., Ikeda, R., Che, X., Ooyama, A., Yamamoto, M., Furukawa, T. ... Akiyama, S. (2013). VEGF expression is augmented by hypoxia‑induced PGIS in human fibroblasts. International Journal of Oncology, 43, 746-754. https://doi.org/10.3892/ijo.2013.1994
MLA
Wang, J., Ikeda, R., Che, X., Ooyama, A., Yamamoto, M., Furukawa, T., Hasui, K., Zheng, C., Tajitsu, Y., Oka, T., Tabata, S., Nishizawa, Y., Eizuru, Y., Akiyama, S."VEGF expression is augmented by hypoxia‑induced PGIS in human fibroblasts". International Journal of Oncology 43.3 (2013): 746-754.
Chicago
Wang, J., Ikeda, R., Che, X., Ooyama, A., Yamamoto, M., Furukawa, T., Hasui, K., Zheng, C., Tajitsu, Y., Oka, T., Tabata, S., Nishizawa, Y., Eizuru, Y., Akiyama, S."VEGF expression is augmented by hypoxia‑induced PGIS in human fibroblasts". International Journal of Oncology 43, no. 3 (2013): 746-754. https://doi.org/10.3892/ijo.2013.1994