Adipokine apelin ameliorates chronic colitis in Il-10-/- mice by promoting intestinal lymphatic functions
Adipokine apelin ameliorates chronic colitis in Il-10-/- mice by promoting intestinal lymphatic functions
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脂肪因子 apelin 通过促进肠道淋巴功能改善 Il-10(-/-) 小鼠的慢性结肠炎
DOI：
10.1016/j.bcp.2018.01.011
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发表时间：
2018-02-01
影响因子：
5.8
通讯作者：
Li, Jieshou
中科院分区：
文献类型：
--
作者：
Ge, Yuanyuan;Li, Yi;Li, Jieshou
肠系膜脂肪组织（MAT）和淋巴管（LV）在克罗恩病（CD）的发病机制中起重要作用，脂肪因子参与MAT和LV之间的相互作用。Apelin是一种新发现的脂肪细胞因子，已被证明在LV的形成和稳定中起着至关重要的作用。我们的目的是确定CD患者MAT中apelin的表达，并探索apelin是否影响小鼠结肠炎的病程，并确定其对LV的贡献。检测CD患者（n = 24）和非CD患者（对照，n = 12）的MAT标本中爱帕琳蛋白的表达。向患有结肠炎的IL-10缺陷型（IL-10（-/-））小鼠施用爱帕琳，未处理的和野生型小鼠作为对照（每组n = 8）。评价疾病活动度和结肠炎症。并对左室密度、淋巴引流功能及相关信号通路进行分析。我们发现CD患者的MAT与对照组相比表达更高水平的apelin。全身递送爱帕琳显著改善了IL-10（-/-）小鼠的慢性结肠炎，表现为疾病活动指数和炎症评分降低，以及TNF-α、IL-1 β和IL-6水平降低。增加的LV密度和podoplanin水平表明，爱帕琳促进淋巴管生成。伊文思蓝染色和荧光淋巴管造影显示apelin处理小鼠的淋巴引流功能增强。发现爱帕琳的作用与Akt和Erk信号通路的激活有关。这些结果表明，脂肪因子apelin在CD患者的MAT中高度表达，并且通过促进肠淋巴功能而在改善实验性结肠炎中具有有希望的作用，这表明在CD状态的MAT中脂肪因子和LV之间存在潜在的串扰。用脂肪因子（如爱帕琳）治疗可能是治疗CD的新方法。(C)2018由Elsevier Inc.出版
Both mesenteric adipose tissue (MAT) and lymphatic vessels (LVs) play important roles in the pathogenesis of Crohn's disease (CD), and adipokines have been implicated in the crosstalk between MAT and LVs. Apelin, a newly identified adipokine, has been demonstrated to be crucial in the development and stabilization of LVs. We aimed to identify the expression of apelin in MAT of CD patients and explore whether apelin influences the disease course in murine colitis and determine its contributions to LVs. Expression of apelin in MAT specimens from patients with CD (n = 24) and without CD (control, n = 12) was detected. Il-10 deficient (Il-10(-/-)) mice with established colitis were administered apelin, and untreated and wild type mice served as controls (n = 8 for each group). Disease activity and colonic inflammation was evaluated. The LV density, lymphatic drainage function and related signaling pathways were also analyzed. We found that MAT from CD patients expressed a higher level of apelin compared with that from controls. Systemic delivery of apelin significantly ameliorated chronic colitis in Il-10(-/-) mice, demonstrated by decreased disease activity index and inflammatory scores, and lower levels of Tnf-alpha, Il-1 beta and Il-6. Increased LV density and podoplanin levels indicated that apelin promoted lymphangiogenesis. Evans blue dye and fluorescent lymphangiography revealed an enhanced lymphatic drainage function in apelin-treated mice. The role of apelin was found to be related to the activation of the Akt and Erk signaling pathways. These results indicate that the adipokine apelin was highly expressed in MAT of CD patients and has a promising role in ameliorating experimental colitis by promoting intestinal lymphatic functions, suggesting the potential crosstalk between adipokines and LVs in MAT in CD status. Therapies with adipokines, such as apelin, may be a novel approach for the treatment of CD. (C) 2018 Published by Elsevier Inc.