Role of thromboxane prostanoid (TP) receptor in the facilitation of angiogenesis and the healing of gastric ulcers

[Speaker] Sakiko Yamane:1,2
[Co-author] Hideki Amano:2, Tomohiro Betto:1,2, Tomoyoshi Inoue:1,2, Yoshiya Ito:2,3, Yuki Shimizu:1,2, Nobuyuki Nishizawa:2,3, Shuh Narumiya:4, Wasaburo Koizumi:1, Masataka Majima:2
1:Department of Gastroenterology, Kitasato University School of Medicine, Japan, 2:Department of pharmacology, Kitasato university, Japan, 3:Department of surgery, Kitasato university, Japan, 4:Medical Innovation Center, Kyoto University Graduate School of Medicine, Japan

Background: Gastric ulcer healing is a complex process, which involves cell migration, proliferation, angiogenesis and re-epithelialization. Platelets contain growth factors that can modulate healing processes, including vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1 (SDF-1). Thromboxane A2 (TXA2) induces platelet adhesion through thromboxane prostanoid (TP) receptor.
However, the precise mechanisms of platelet-dependent mucosa healing, especially the involvement of TP signaling, has not been fully elucidated. The present study hypothesized that TXA2-TP signaling contributes to healing of gastric ulcer.

Methods: Male 6-8 weeks old C57Bl/6 (Wild type=WT) and TP knock out mice (TPKO) were used. Gastric ulcers were induced by serosal application of 100 % acetic acid in WT and TPKO and the areas of the ulcers were measured on day 7. Angiogenesis was estimated by determining the number of CD31 (+) vessels by immunohistochemical analysis. The expression of pro-angiogenic factors was quantified by real time PCR.

Results: Gastric Ulcer healing was delayed in TXA2 receptor antagonist (S-1452) and the TXA2 synthase inhibitor (OKY-046) compared with control mice. TPKO significantly delayed ulcer healing compared to WT. The expression of CD31 around ulcer area and this was significantly suppressed in TPKO (P<0.05). Furthermore, the mRNA level of pro-angiogenic factors, TGF-b, VEGF, and SDF-1, in ulcer area was significantly suppressed in TPKO (P<0.05).
Conclusions: These results suggested that TXA2-TP signaling - signaling plays a critical role in gastric ulcer healing.

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