The role of thromboxane prostanoid receptor signaling in gastric ulcer healing

IF 1.8 4区医学 Q3 PATHOLOGY International Journal of Experimental Pathology Pub Date : 2021-10-16 DOI:10.1111/iep.12410

Sakiko Yamane, Hideki Amano, Yoshiya Ito, Tomohiro Betto, Yoshio Matsui, Wasaburo Koizumi, Shuh Narumiya, Masataka Majima

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引用次数: 6

Abstract

The process of gastric ulcer healing includes cell migration, proliferation, angiogenesis and re-epithelialization. Platelets contain angiogenesis stimulating factors that induce angiogenesis. Thromboxane A₂ (TXA₂) not only induces platelet activity but also angiogenesis. This study investigated the role of TXA₂ in gastric ulcer healing using TXA₂ receptor knockout (TPKO) mice. Gastric ulcer healing was suppressed by treatment with the TXA₂ synthase inhibitor OKY-046 and the TXA₂ receptor antagonist S-1452 compared with vehicle-treated mice. TPKO showed delayed gastric ulcer healing compared with wild-type mice (WT). The number of microvessels and CD31 expression were lower in TPKO than in WT mice, and TPKO suppressed the expression of transforming growth factor beta (TGF-β) and vascular endothelial growth factor A (VEGF-A) in areas around gastric ulcers. Immunofluorescence assays showed that TGF-β and VEGF-A co-localized with platelets. Gastric ulcer healing was significantly reduced in WT mice transplanted with TPKO compared with WT bone marrow. These results suggested that TP signalling on platelets facilitates gastric ulcer healing through TGF-β and VEGF-A.

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血栓素前列腺素受体信号在胃溃疡愈合中的作用

胃溃疡的愈合过程包括细胞迁移、增殖、血管生成和再上皮化。血小板含有血管生成刺激因子，可诱导血管生成。血栓素A2 (TXA2)不仅能诱导血小板活性，还能促进血管生成。本研究利用TXA2受体敲除(TPKO)小鼠研究了TXA2在胃溃疡愈合中的作用。与对照组相比，TXA2合成酶抑制剂OKY-046和TXA2受体拮抗剂S-1452可抑制小鼠胃溃疡愈合。与野生型小鼠(WT)相比，TPKO显示胃溃疡愈合延迟。TPKO小鼠的微血管数量和CD31表达均低于WT小鼠，TPKO抑制胃溃疡周围区域转化生长因子β (TGF-β)和血管内皮生长因子A (VEGF-A)的表达。免疫荧光检测显示TGF-β和VEGF-A与血小板共定位。与WT骨髓相比，TPKO移植的WT小鼠胃溃疡愈合明显减少。这些结果表明，血小板上的TP信号通过TGF-β和VEGF-A促进胃溃疡愈合。

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来源期刊

International Journal of Experimental Pathology 医学-病理学

CiteScore

4.50

自引率

3.30%

发文量

审稿时长

>12 weeks

期刊介绍： Experimental Pathology encompasses the use of multidisciplinary scientific techniques to investigate the pathogenesis and progression of pathologic processes. The International Journal of Experimental Pathology - IJEP - publishes papers which afford new and imaginative insights into the basic mechanisms underlying human disease, including in vitro work, animal models, and clinical research. Aiming to report on work that addresses the common theme of mechanism at a cellular and molecular level, IJEP publishes both original experimental investigations and review articles. Recent themes for review series have covered topics as diverse as "Viruses and Cancer", "Granulomatous Diseases", "Stem cells" and "Cardiovascular Pathology".