The role of Angiotensin II type 1A receptor signaling in gastric ulcer healing

[Background]: Gastric ulcer is a chronic disease featured with repeated healing and recurrence. Angiogenesis is one of important factors for the healing process. Angiotensin II (ANG II) involves in cell proliferation and tissue repair. The objective of this study is to evaluate the role of ANG II type 1A on gastric ulcer healing. [Methods and Results]: Gastric ulcers were induced by the serosal application of 100% acetic acid. The gastric ulcerated areas were significantly enlarged in mice treated with ANG II type 1 receptor (AT1) blocker (ARB) compared to those in vehicle-treated mice. The number of cluster of differentiation (CD31) positive cells in the ulcerated area was lower in ARB-treated mice. There was prolonged gastric healing in the AT1a knock out (KO) mice compared to that in the wild-type (WT) mice. The mRNA (messenger RNA) levels of transforming growth factor-β (TGF-β) and stromal cell derived factor-1 (SDF-1) in the ulcerated area were significantly suppressed in AT1aKO mice compared to those in WT mice. The number of accumulated CD11b+ cells, the marker for macrophages, in the ulcer granulation was lower in AT1aKO mice. Furthermore, immunofluorescence analysis revealed that CD11b+ macrophages co-stained with SDF-1 and TGF-β in the ulcerated area in WT mice had increased compared with those in AT1aKO mice. [Conclusion]: These results suggested that ANG II-AT1a signaling induces gastric ulcer healing by TGF-β and SDF-1 production from accumulated macrophages.