Adiponectin deficiency protects mice from chemically induced colonic inflammation
Adiponectin deficiency protects mice from chemically induced colonic inflammation
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DOI：
10.1053/j.gastro.2006.11.026
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发表时间：
2007-02-01
期刊：
影响因子：
29.4
通讯作者：
Fantuzzi, Giamila
中科院分区：
文献类型：
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作者：
Fayad, Raja;Pini, Maria;Fantuzzi, Giamila
背景与目的：脂联素（APN）是一种调节胰岛素敏感性的脂肪因子，在动脉粥样硬化中具有抗炎作用。本研究的目的是探讨APN在肠道炎症中的作用。研究方法：APN敲除（KO）小鼠及其野生型（WT）同窝出生的小鼠接受葡聚糖硫酸钠（DSS）或三硝基苯磺酸（TNBS）以诱导肠道炎症。评估临床和组织学评分以及上皮细胞增殖。检测细胞因子和APN水平。免疫组化法检测APN和肝素结合表皮生长因子（HB-EGF）的表达。APN及其受体，HB-EGF，和碱性成纤维细胞生长因子（bFGF）信使RNA的表达进行了评估，通过逆转录聚合酶链反应。用免疫共沉淀法研究血清APN与HB-EGF、bFGF的关系。结果：APN KO小鼠免受化学诱导的结肠炎;给予APN恢复炎症。APN在结肠中表达，管腔APN与结肠上皮细胞缔合。在体外，APN增加结肠组织中促炎细胞因子的产生。APN的表达与bFGF和HB-EGF的表达重叠，在结肠炎中起保护作用。循环APN与bFGF和HB-EGF结合，可能抑制其保护活性。抑制HB-EGF生物活性所需的EGF受体信号传导，可恢复APN KO小鼠的炎症。结论：APN缺乏与化学诱导的结肠炎的保护有关。APN通过诱导促炎细胞因子的产生和抑制保护性生长因子的生物活性而在结肠中发挥促炎活性。因此，在结肠炎中，APN发挥与动脉粥样硬化相反的作用。
Background & Aim: Adiponectin (APN) is an adipokine that regulates insulin sensitivity and is anti-inflammatory in atherosclerosis. The goal of this study was to investigate the role of APN in intestinal inflammation. Methods: APN knockout (KO) mice and their wild-type (WT) littermates received dextran sulfate sodium (DSS) or trinitrobenzene sulfonic acid (TNBS) to induce intestinal inflammation. Clinical and histologic scores and proliferation of epithelial cells were assessed. Cytokines and APN levels were measured. Expression of APN and heparin binding epidermal growth factor (HB-EGF) was analyzed by immunohistochemistry. Expression of APN and its receptors, HB-EGF, and basic fibroblast growth factor (bFGF) messenger RNA was assessed by reverse-transcription polymerase chain reaction. Association of serum APN with HB-EGF and bFGF was studied by coimmunoprecipitation. Results: APN KO mice are protected from chemically induced colitis; administration of APN restores inflammation. APN is expressed in the colon, luminal APN associates with colonic epithelial cells. In vitro, APN increases production of proinflammatory cytokines from colonic tissue. Expression of colonic APN overlaps with that of bFGF and HB-EGF, which play a protective role in colitis. Circulating APN binds to bFGF and HB-EGF, likely inhibiting their protective activity. Inhibition of EGF receptor signaling, which is required for biologic activity of HB-EGF, restores inflammation in APN KO mice. Conclusions: APN deficiency is associated with protection from chemically induced colitis. APN exerts proinflammatory activities in the colon by inducing production of proinflammatory cytokines and inhibiting bioactivity of protective growth factors. Thus, in colitis, APN exerts an opposite role compared with atherosclerosis.