The role of thromboxane prostanoid receptor signaling in gastric ulcer healing

• Published in: International journal of experimental pathology Vol. 103; no. 1; pp. 4 - 12
• Main Authors: Yamane, Sakiko, Amano, Hideki, Ito, Yoshiya, Betto, Tomohiro, Matsui, Yoshio, Koizumi, Wasaburo, Narumiya, Shuh, Majima, Masataka
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.02.2022; John Wiley and Sons Inc
• Subjects: Angiogenesis; Animals; Bone marrow; Bone marrow transplantation; Cell migration; gastric ulcer healing; Growth factors; Healing; Immunofluorescence; Mice; Mice, Inbred C57BL; Neovascularization, Pathologic - metabolism; Original; Platelet Activation - drug effects; Platelets; Prostaglandins - pharmacology; Receptors; Receptors, Thromboxane - drug effects; Rodents; Signal Transduction - drug effects; Signaling; Stomach Ulcer - drug therapy; Stomach Ulcer - metabolism; TGF‐β; Thromboxane A2; Thromboxanes - pharmacology; Transforming growth factor-b; TXA2; Ulcers; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism; VEGF‐A; Wound Healing - drug effects; TGF-β; TXA2; gastric ulcer healing; VEGF-A; angiogenesis
• ISSN: 0959-9673; 1365-2613
• DOI: 10.1111/iep.12410

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.