Leptin Promotes Gastric Ulcer Healing via Upregulation of Vascular Endothelial Growth Factor
Leptin Promotes Gastric Ulcer Healing via Upregulation of Vascular Endothelial Growth Factor
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DOI：
10.1159/000243719
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发表时间：
2010-01-01
期刊：
影响因子：
3.2
通讯作者：
Arakawa, Tetsuo
中科院分区：
文献类型：
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作者：
Tanigawa, Tetsuya;Watanabe, Toshio;Arakawa, Tetsuo
背景与目的：瘦素是调节食物摄入和能量消耗的关键激素，具有多效的类瘦素生物学效应。其在胃溃疡愈合中的作用尚不清楚。在这项研究中，我们研究了瘦素在胃溃疡愈合中的作用。方法：采用醋酸局部灌胃法，建立瘦素缺陷型ob/ob小鼠和野生型小鼠实验性胃溃疡模型。评价胃溃疡愈合和溃疡组织中的血管生成。结果：ob/ob小鼠胃溃疡愈合较野生型小鼠延迟。在ob/ob小鼠中观察到的溃疡愈合受损的特征在于血管内皮生长因子（VEGF）表达减少和血管生成受损。全身性给予瘦素的ob/ob小鼠逆转胃溃疡愈合的损害，这种逆转伴随着VEGF表达和血管生成的增加。虽然瘦素的mRNA在正常胃粘膜中不表达，在溃疡组织中不诱导，但瘦素受体在溃疡边缘的胃上皮细胞中表达显著上调，并与VEGF共定位。结论：这些发现表明，瘦素通过上调VEGF表达诱导溃疡颗粒组织中的血管生成来促进胃溃疡愈合。版权所有（C）2010 S. Karger AG，巴塞尔
Background and Aim: Leptin, a key hormone in regulation of food intake and energy expenditure, exerts pleiotropic cytokine-like biological effects. Its role in gastric ulcer healing is unclear. In this study, we investigated the role of leptin in gastric ulcer healing. Methods: Experimental gastric ulcer was induced by focal serosal application of acetic acid in leptin-deficient ob/ob mice and wild-type mice. Healing of gastric ulcer and angiogenesis in the ulcer tissue was evaluated. Results: Gastric ulcer healing was delayed in ob/ob mice compared with that in wild-type mice. The impairment of ulcer healing observed in ob/ob mice was characterized by reduced expression of vascular endothelial growth factor (VEGF) and impairment of angiogenesis. Systemic administration of leptin to ob/ob mice reversed the impairment of gastric ulcer healing; this reversal was accompanied by an increase in VEGF expression and angiogenesis. Although mRNA for leptin was not expressed in normal gastric mucosa and not induced in ulcerous tissue, leptin receptor expression was markedly upregulated in gastric epithelial cells at ulcer margins, and was colocalized with VEGF. Conclusion: These findings suggest that leptin promotes gastric ulcer healing by induction of angiogenesis in the granular tissue of ulcers via upregulation of VEGF expression. Copyright (C) 2010 S. Karger AG, Basel