TLR9 is important for protection against intestinal damage and for intestinal repair.
TLR9 is important for protection against intestinal damage and for intestinal repair.
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DOI：
10.1038/srep00574
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发表时间：
2012
影响因子：
4.6
通讯作者：
Leifer, Cynthia Anne
中科院分区：
文献类型：
--
作者：
Rose, William Alfred, II;Sakamoto, Kaori;Leifer, Cynthia Anne
toll样受体（TLRs）是对宿主防御至关重要的先天受体，在正常的生物过程中发挥作用。例如，宿主DNA，一种TLR9配体，刺激皮肤损伤后的上皮修复。TLR信号在调节肠道稳态中也起着至关重要的作用。因此，我们使用葡聚糖硫酸钠（DSS）诱导的肠道损伤和修复模型来研究TLR9是否在肠道伤口修复中起重要作用。我们发现tlr9缺陷小鼠更容易发生DSS，并且在临床和组织学水平上都表现出延迟的伤口修复。tlr9缺陷小鼠的分裂1毛增强子（一种肠道祖细胞分化因子）和血管内皮生长因子（一种对上皮细胞修复有重要作用的生长因子）的基因表达降低。因此，我们认为TLR刺激可能在调节肠道稳态中发挥正常作用，并可能成为炎症性肠病中促进肠道伤口修复的新治疗靶点。
Toll-like receptors (TLRs) are innate receptors critical for host defense, and play a role in normal biological processes. For example, host DNA, a TLR9 ligand, stimulates epithelial repair following skin wounding. TLR signaling also plays a crucial role in regulating intestinal homeostasis. We therefore asked whether TLR9 is important for intestinal wound repair using a dextran sulfate sodium (DSS)-induced intestinal damage and repair model. We showed that TLR9-deficient mice are more susceptible to DSS, and exhibited delayed wound repair at both the clinical and histologic levels. TLR9-deficient mice showed reduced gene expression of hairy enhancer of split 1, an intestinal progenitor cell differentiation factor, and vascular endothelial growth factor, a growth factor important for epithelial cell restitution. Therefore, we conclude that TLR stimulation may play a normal role in regulating intestinal homeostasis and could potentially be a novel therapeutic target to enhance intestinal wound repair in inflammatory bowel diseases.
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