The role of thromboxane prostanoid receptor signaling in gastric ulcer healing.

The role of thromboxane prostanoid receptor signaling in gastric ulcer healing.
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血栓烷前列腺素受体信号传导在胃溃疡愈合中的作用。

DOI:
10.1111/iep.12410
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发表时间:
2022-03
影响因子:
3
通讯作者:
Majima M
Majima M
中科院分区:
医学4区
文献类型:
--
作者:
Yamane S;Amano H;Ito Y;Betto T;Matsui Y;Koizumi W;Narumiya S;Majima M

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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。与对照剂处理的小鼠相比,TXA2合成酶抑制剂OKY‐046和TXA2受体拮抗剂S‐1452可抑制胃溃疡愈合。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。免疫荧光分析显示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。
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.
DOI: 10.1254/jjp.79.101
发表时间: 1999-01-01
期刊: JAPANESE JOURNAL OF PHARMACOLOGY
影响因子: --
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发表时间: 2005-08-19
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发表时间: 1998-03
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