The role of thromboxane prostanoid receptor signaling in gastric ulcer healing

The process of gastric ulcer healing includes cell migration, proliferation, angiogenesis and re‐epithelialization. Platelets contain angiogenesis stimulating factors that induce angiogenesis. Thromboxane A(2) (TXA(2)) not only induces platelet activity but also angiogenesis. This study investigated the role of TXA(2) in gastric ulcer healing using TXA(2) receptor knockout (TPKO) mice. Gastric ulcer healing was suppressed by treatment with the TXA(2) synthase inhibitor OKY‐046 and the TXA(2) 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.