Protective Role of Adiponectin Against Ethanol Induced Gastric Injury in Mice

Abstract

19 Adiponectin is an anti-inflammatory molecule released from adipocytes, and serum adiponectin 20 concentrations are reduced in obesity. We previously reported that gastric erosion occurs in 21 association with obesity and low serum adiponectin levels. In the present study, we examined 22 adiponectin-knockout (APN-KO) mice to elucidate the role of adiponectin in gastric mucosal 23 injury. Gastric injury was induced by oral administration of ethanol in wild-type (WT) and 24 APN-KO mice. Ethanol treatment induced severe gastric injury in APN-KO mice compared with 25 WT mice. In APN-KO mice, increased apoptotic cells and decreased expression of prostaglandin 26 E2 (PGE2) were detected in the injured stomach. We next assessed the effect of adiponectin on 27 the cellular response to ethanol treatment and wound repair in rat gastric mucosal cells (RGM1). 28 Adiponectin induced the expression of PGE2 and cyclooxygenase 2 (COX-2) in ethanol-treated 29 RGM1 cells. RGM1 cells exhibited efficient wound repair accompanied by increased PGE2 30 expression in the presence of adiponectin. Co-administration of adiponectin with celecoxib, a 31 COX-2 inhibitor, inhibited efficient wound repair. These findings indicate that adiponectin has a 32 protective role against ethanol-induced gastric mucosal injury in mice. This effect may be 33 partially mediated by the efficient wound repair of epithelial cells via increased PGE2 expression. 34 35