Aspirin delays the healing of acetic acid-induced gastric ulcer with attenuated recruitment of hematopoietic progenitor cells to ulcer granulation tissue in mice

Objective: To examine how aspirin affects the healing of gastric ulcer and angiogenesis. Hematopoietic progenitor cells expressing vascular endothelial growth factor receptor-1 (VEGFR1) promote angiogenesis. We examined the involvement of progenitor cells during the process of ulcer healing. Methods: Gastric ulcers were induced by the serosal application of 100% acetic acid in mice treated with aspirin (100 mg/kg, daily) or vehicle in wild-type (WT) and tyrosine kinase-deficient VEGFR1 mice (VEGFR1 TKKO). Results: Treatment with aspirin delayed ulcer healing and inhibited angiogenesis. Aspirin suppressed the mobilization of progenitor cells expressing CXCR4 VEGFR1 cells in circulation and the recruitment of these cells in ulcer granulation tissue. Ulcer healing and recruitment of CXCR4 VEGFR1 cells were impaired in VEGFR1 TKKO as compared with WT mice. The plasma level of stromal cell-derived factor-1 and stem cell factor and bone marrow level of pro-MMP9 (pro-matrix metalloproteinase 9) were significantly reduced in VEGFR1 TKKO mice. Treatment with aspirin in VEGFR1 TKKO mice did not further interfere with the ulcer healing compared to vehicle treatment. Conclusion: These results for aspirin were not conclusive; however, VEGFR1 signaling is required for healing of acetic acid-induced gastric ulcer with increased recruitment of progenitor cells to ulcer granulation tissue.

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