Galectin-2 and -4, But Not Galectin-1, Promote Intestinal Epithelial Wound Healing In Vitro Through a TGE-beta-independent Mechanism
Galectin-2 and -4, But Not Galectin-1, Promote Intestinal Epithelial Wound Healing In Vitro Through a TGE-beta-independent Mechanism
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DOI：
10.1002/ibd.20499
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发表时间：
2008-10-01
影响因子：
4.9
通讯作者：
Sturm, Andreas
中科院分区：
文献类型：
--
作者：
Paclik, Daniela;Lohse, Katrin;Sturm, Andreas
背景资料：炎症性肠病（IBD）的特征在于不同程度的粘膜表面损伤和随后的肠屏障功能受损。上皮屏障屏障的重新密封需要肠细胞迁移和增殖。半乳糖凝集素越来越多地被认为是一种新型的炎症调节剂。因此，我们的目的是探讨半乳糖凝集素-2（Gal-2）和Gal-4对上皮细胞功能和伤口愈合的影响。Gal-1的细胞迁移。-2.和-4通过愈合试验测定。结果：Gal-2和Gal-4在E-cadherin/beta-catenin复合物的作用下后移于上皮细胞。两种半乳糖凝集素均显著增强体外肠上皮细胞恢复。这种上皮细胞恢复的增强是TGF-β非依赖性的。相反。Gal-1依赖性地减少上皮细胞迁移。进行细胞周期分析。我们发现Gal-2和Gal-4增加了细胞周期蛋白B1的表达，从而增加了细胞周期进程。Gal-1抑制细胞周期。确定Gal-2和Gal-4对上皮细胞凋亡的影响，我们显示没有诱导凋亡。结论：Gal-2和Gal-4与肠上皮细胞结合，促进肠上皮细胞的修复。因此。我们的研究首次提供了这些半乳糖凝集素在肠创伤愈合过程中起重要作用的证据，并且可能在以上皮屏障破坏为特征的疾病如IBD中发挥有益作用。（Inflamm Bowel Dis 2008; 14：1366-1372）
Background: Inflammatory bowel diseases (IBDs) are characterized by various degrees of mucosal surface damage and subsequent impairment of the intestinal barrier function. Resealing of epithelial barrier harrier requires intestinal cell migration and proliferation. Galectins are increasingly recognized as novel regulators of inflammation. Thus, we aimed to explore the effect of galectin-2 (Gal-2) and Gal-4 on epithelial cell function and Wound healing.Methods: Binding of Gal-2 and Gal-4 was determined by flow cytometric analysis and binding sites by SDS-PAGE electrophoresis. Cell migration by Gal-1. -2. and -4 was determined by a would-healing assay. Cell cycle analysis stud detection of apoptosis were determined by flow cytometric analysis.Results: Gal-2 and Gal-4 hind to epithelial cells at the E-cadherin/beta-catenin complex. Both galectins significantly enhanced intestinal epithelial cell restitution in vitro. This enhancement of epithelial cell restitution was TGF-beta-independent. In contrast. Gal-1 decreased epithelial cell migration TGF-beta dependently. By performing cell cycle analysis. we show that Gal-2 and Gal-4 increased cyclin B1 expression and consequently cell cycle progression. while Gal-1 inhibited cell cycling. Determining the influence of Gal-2 and Gal-4 on epithelial cell apoptosis, we showed no induction of apoptosis. Whereas Gal-1 significantly induced apoptosis of epithelial cells caspase-independently.Conclusions: Gal-2 and Gal-4 bind to intestinal epithelial cells and promote their restitution. Thus. our study provides for the first time evidence that these galectins play a significant role in intestinal wound-healing processes and might exert beneficial effects in diseases characterized by epithelial harrier disruption like IBDs. (Inflamm Bowel Dis 2008; 14:1366-1372)