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Inhibition of TP signaling promotes endometriosis growth and neovascularization

  • Authors:
    • Akiko Furue
    • Kyoko Hattori
    • Kanako Hosono
    • Mina Tanabe
    • Erina Sato
    • Masako Honda
    • Kazuki Sekiguchi
    • Yoshiya Ito
    • Masataka Majima
    • Shuh Narumiya
    • Kazuyoshi Kato
    • Hideki Amano
  • View Affiliations / Copyright

    Affiliations: Department of Molecular Pharmacology, Graduate School of Medical Sciences, Sagamihara, Kanagawa 252‑0374, Japan, Department of Obstetrics and Gynecology, Kitasato University School of Medicine, Sagamihara, Kanagawa 252‑0374, Japan, Department of Medical Therapeutics, Kanagawa Institute of Technology, Atsugi, Kanagawa 243‑0292, Japan, Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606‑8507, Japan
    Copyright: © Furue et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 192
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    Published online on: August 30, 2023
       https://doi.org/10.3892/mmr.2023.13079
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Abstract

Endometriosis is highly dependent on angiogenesis and lymphangiogenesis. Prostaglandin E2, an arachidonic acid metabolite, has been shown to promote the formation of new blood and lymphatic vessels. However, the role of another arachidonic acid metabolite, thromboxane A2 (TXA2) in angiogenesis and lymphangiogenesis during endometriosis remains largely unexplored. Using a murine model of ectopic endometrial transplantation, fragments from the endometrium of WT donor mice were transplanted into the peritoneal walls of recipient WT mice (WT→WT), resulting in an increase in both the area and density of blood and lymphatic vessels. Upon transplantation of endometrial tissue from thromboxane prostanoid (TP) receptor (TXA2 receptor)‑deficient (TP‑/‑) mice into TP‑/‑ mice (TP‑/‑→TP‑/‑), an increase in implant growth, angiogenesis, and lymphangiogenesis were observed along with upregulation of pro‑angiogenic and lymphangiogenic factors, including vascular endothelial growth factors (VEGFs). Similar results were obtained using a thromboxane synthase (TXS) inhibitor in WT→WT mice. Furthermore, TP‑/‑→TP‑/‑ mice had a higher number of F4/80+ cells than that of WT→WT mice, with increased expression of genes related to the anti‑inflammatory macrophage phenotype in endometrial lesions. In cultured bone marrow (BM)‑derived macrophages, the levels of VEGF‑A, VEGF‑C, and VEGF‑D decreased in a TP‑dependent manner. Furthermore, TP signaling affected the polarization of cultured BM‑derived macrophages to the anti‑inflammatory phenotype. These findings imply that inhibition of TP signaling promotes endometrial implant growth and neovascularization.
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Copy and paste a formatted citation
Spandidos Publications style
Furue A, Hattori K, Hosono K, Tanabe M, Sato E, Honda M, Sekiguchi K, Ito Y, Majima M, Narumiya S, Narumiya S, et al: Inhibition of TP signaling promotes endometriosis growth and neovascularization. Mol Med Rep 28: 192, 2023.
APA
Furue, A., Hattori, K., Hosono, K., Tanabe, M., Sato, E., Honda, M. ... Amano, H. (2023). Inhibition of TP signaling promotes endometriosis growth and neovascularization. Molecular Medicine Reports, 28, 192. https://doi.org/10.3892/mmr.2023.13079
MLA
Furue, A., Hattori, K., Hosono, K., Tanabe, M., Sato, E., Honda, M., Sekiguchi, K., Ito, Y., Majima, M., Narumiya, S., Kato, K., Amano, H."Inhibition of TP signaling promotes endometriosis growth and neovascularization". Molecular Medicine Reports 28.4 (2023): 192.
Chicago
Furue, A., Hattori, K., Hosono, K., Tanabe, M., Sato, E., Honda, M., Sekiguchi, K., Ito, Y., Majima, M., Narumiya, S., Kato, K., Amano, H."Inhibition of TP signaling promotes endometriosis growth and neovascularization". Molecular Medicine Reports 28, no. 4 (2023): 192. https://doi.org/10.3892/mmr.2023.13079
Copy and paste a formatted citation
x
Spandidos Publications style
Furue A, Hattori K, Hosono K, Tanabe M, Sato E, Honda M, Sekiguchi K, Ito Y, Majima M, Narumiya S, Narumiya S, et al: Inhibition of TP signaling promotes endometriosis growth and neovascularization. Mol Med Rep 28: 192, 2023.
APA
Furue, A., Hattori, K., Hosono, K., Tanabe, M., Sato, E., Honda, M. ... Amano, H. (2023). Inhibition of TP signaling promotes endometriosis growth and neovascularization. Molecular Medicine Reports, 28, 192. https://doi.org/10.3892/mmr.2023.13079
MLA
Furue, A., Hattori, K., Hosono, K., Tanabe, M., Sato, E., Honda, M., Sekiguchi, K., Ito, Y., Majima, M., Narumiya, S., Kato, K., Amano, H."Inhibition of TP signaling promotes endometriosis growth and neovascularization". Molecular Medicine Reports 28.4 (2023): 192.
Chicago
Furue, A., Hattori, K., Hosono, K., Tanabe, M., Sato, E., Honda, M., Sekiguchi, K., Ito, Y., Majima, M., Narumiya, S., Kato, K., Amano, H."Inhibition of TP signaling promotes endometriosis growth and neovascularization". Molecular Medicine Reports 28, no. 4 (2023): 192. https://doi.org/10.3892/mmr.2023.13079
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