Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan.
Am J Physiol Gastrointest Liver Physiol. 2012 Apr 15;302(8):G773-80. doi: 10.1152/ajpgi.00324.2011. Epub 2012 Feb 9.
Adiponectin is an anti-inflammatory molecule released from adipocytes, and serum adiponectin concentrations are reduced in obesity. We previously reported that gastric erosion occurs in association with obesity and low serum adiponectin levels. In the present study, we examined adiponectin-knockout (APN-KO) mice to elucidate the role of adiponectin in gastric mucosal injury. Gastric injury was induced by oral administration of ethanol in wild-type (WT) and APN-KO mice. Ethanol treatment induced severe gastric injury in APN-KO mice compared with WT mice. In APN-KO mice, increased apoptotic cells and decreased expression of prostaglandin E(2) (PGE(2)) were detected in the injured stomach. We next assessed the effect of adiponectin on the cellular response to ethanol treatment and wound repair in rat gastric mucosal cells (RGM1). Adiponectin induced the expression of PGE(2) and cyclooxygenase 2 (COX-2) in ethanol-treated RGM1 cells. RGM1 cells exhibited efficient wound repair accompanied by increased PGE(2) expression in the presence of adiponectin. Coadministration of adiponectin with celecoxib, a COX-2 inhibitor, inhibited efficient wound repair. These findings indicate that adiponectin has a protective role against ethanol-induced gastric mucosal injury in mice. This effect may be partially mediated by the efficient wound repair of epithelial cells via increased PGE(2) expression.
脂联素是一种由脂肪细胞释放的抗炎分子,肥胖患者的血清脂联素浓度降低。我们之前的研究报告表明,肥胖和低血清脂联素水平与胃侵蚀有关。在本研究中,我们检查了脂联素敲除(APN-KO)小鼠,以阐明脂联素在胃黏膜损伤中的作用。在野生型(WT)和 APN-KO 小鼠中,通过口服乙醇诱导胃损伤。与 WT 小鼠相比,APN-KO 小鼠中乙醇处理诱导的严重胃损伤。在 APN-KO 小鼠中,损伤胃中检测到凋亡细胞增加和前列腺素 E2(PGE2)表达减少。接下来,我们评估了脂联素对乙醇处理和大鼠胃黏膜细胞(RGM1)伤口修复中细胞反应的影响。脂联素诱导乙醇处理的 RGM1 细胞中 PGE2 和环氧化酶 2(COX-2)的表达。在脂联素存在的情况下,RGM1 细胞表现出有效的伤口修复,并伴随着 PGE2 表达的增加。脂联素与 COX-2 抑制剂塞来昔布共同给药可抑制有效的伤口修复。这些发现表明脂联素在小鼠中具有抵抗乙醇诱导的胃黏膜损伤的保护作用。这种作用可能部分是通过增加 PGE2 表达来实现上皮细胞的有效伤口修复。