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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。

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

机构信息

Department of Pharmacology, Thoracic Surgery Kitasato University School of Medicine, Kanagawa, Japan.

Department of Gastroenterology, Thoracic Surgery Kitasato University School of Medicine, Kanagawa, Japan.

出版信息

Int J Exp Pathol. 2022 Feb;103(1):4-12. doi: 10.1111/iep.12410. Epub 2021 Oct 16.

DOI:10.1111/iep.12410
PMID:34655121
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8781669/
Abstract

The process of gastric ulcer healing includes cell migration, proliferation, angiogenesis and re-epithelialization. Platelets contain angiogenesis stimulating factors that induce angiogenesis. Thromboxane A (TXA ) not only induces platelet activity but also angiogenesis. This study investigated the role of TXA in gastric ulcer healing using TXA receptor knockout (TPKO) mice. Gastric ulcer healing was suppressed by treatment with the TXA synthase inhibitor OKY-046 and the TXA 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.

摘要

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。血小板含有诱导血管生成的血管生成刺激因子。血栓素 A（TXA）不仅诱导血小板活性，还诱导血管生成。本研究使用血栓素 A 受体敲除（TPKO）小鼠研究 TXA 在胃溃疡愈合中的作用。与给予 vehicle 的小鼠相比，给予 TXA 合酶抑制剂 OKY-046 和 TXA 受体拮抗剂 S-1452 治疗可抑制胃溃疡愈合。与野生型（WT）小鼠相比，TPKO 显示出延迟的胃溃疡愈合。微血管数量和 CD31 表达在 TPKO 中低于 WT 小鼠，并且 TPKO 抑制了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 骨髓移植的 WT 小鼠相比，WT 小鼠的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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18bc/8781669/e29e74682457/IEP-103-4-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18bc/8781669/76895f2da401/IEP-103-4-g004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18bc/8781669/4864fd68e5d1/IEP-103-4-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18bc/8781669/a3280947d6b5/IEP-103-4-g005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18bc/8781669/76895f2da401/IEP-103-4-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18bc/8781669/8799a5a52acd/IEP-103-4-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18bc/8781669/b9ea317a54cb/IEP-103-4-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18bc/8781669/aa947c6d58f1/IEP-103-4-g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18bc/8781669/a3280947d6b5/IEP-103-4-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18bc/8781669/e29e74682457/IEP-103-4-g006.jpg

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