| 抄録 |
Prostanoids play important roles in modulation of gastric mucosal integrity. Prostacycline（PGI2）exhibits protective actions against ethanol-induced gastric mucosal damages via the interactions of neuronal systems. This protective action is closely related to the release of an endogenous neuropeptide, calcitonin gene-related peptide（CGRP）. Further, some of the prostanoids including PGE2 have proangiogenic activties, and enhance the healing from gastric ulcers. A down stream molecule of cyclooxygenase-2 in PG biosynthesis, mPGES-1, an inducible PGE synthase is a key regulator of pathological angiogenesis, and mPGES-1 knockout mice shows the delayed healing from gastric ulcers and reductions in angiogenesis in ulcer granulation tissues. PGE receptor signaling that elevates intracellular cAMP is relevant to the induction of a potent proangiogenic factor, vascular endothelial growth factor（VEGF）. The healing of gastric ulcers and the accumulation of the progenitor cells expressing VEGF type 1 receptor（VEGFR1）were significantly suppressed in aspirin-treated mice with the reductions in angiogenesis. The healing of ulcers was significantly suppressed in VEGFR1 tyrosine kinase-knockout mice（VEGFR1 TKKO）, compared with wild type mice. The plasma levels of SDF-1 and stem cell factor, and bone marrow levels of pro-matrix metallopeptidase 9 were significantly reduced in VEGFR1 TKKO. In VEGFR1 TKKO, the recruitment of the progenitor cells expressing VEGFR1 from bone marrow into the ulcer granulation tissues was suppressed. These results suggest that prostanoids are relevant to the maintenance of gastric mucosal integrity and the healing of gastric ulcers via enhancement of angiogenesis. |
