Open Access

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

  • Published online on: August 30, 2023     https://doi.org/10.3892/mmr.2023.13079
  • Article Number: 192
  • Copyright: © Furue et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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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October-2023
Volume 28 Issue 4

Print ISSN: 1791-2997
Online ISSN:1791-3004

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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