CD47 is a negative regulator of intestinal epithelial cell self-renewal following DSS-induced experimental colitis
CD47 is a negative regulator of intestinal epithelial cell self-renewal following DSS-induced experimental colitis
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DOI：
10.1038/s41598-020-67152-w
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发表时间：
2020-06-23
影响因子：
4.6
通讯作者：
Zen, Ke
中科院分区：
文献类型：
--
作者：
He, Yueqin;Sun, Xinlei;Zen, Ke
CD47缺陷小鼠对葡聚糖硫酸钠（DSS）诱导的实验性结肠炎具有抗性。然而，其潜在的机制仍不完全清楚。在这项研究中，我们描述了CD47在调节胃肠道稳态中的作用。我们发现，与正常情况下相比，人类和小鼠肠上皮中CD47的表达在结肠炎条件下均上调。与此一致，CD47缺乏保护小鼠免受dss诱导的结肠炎。基于肠道类器官和培养细胞的分析表明，CD47缺乏加速了肠上皮细胞的增殖和迁移。机制上，western blot和功能分析表明，CD47缺乏促进小鼠肠上皮细胞在细胞损伤后的增殖和迁移可能是通过上调四种山中转录因子Oct4、Sox2、Klf4和c-Myc（简称OSKM）的表达。因此，我们的研究表明，CD47通过下调OSKM转录因子，在结肠炎期间作为肠上皮细胞更新的负调节因子。
CD47 deficient mice are resistant to dextran sulfate sodium (DSS)-induced experimental colitis. The underlying mechanism, however, remains incompletely understood. In this study, we characterized the role of CD47 in modulating homeostasis of gastrointestinal tract. We found that CD47 expression in both human and mouse intestinal epithelium was upregulated in colitic condition compared to that under normal condition. In line with this, CD47 deficiency protected mice from DSS-induced colitis. Analysis based on both intestinal organoid and cultured cell assays showed that CD47 deficiency accelerated intestinal epithelial cell proliferation and migration. Mechanistically, western blot and functional assays indicated that CD47 deficiency promoting mouse intestinal epithelial cell proliferation and migration follow cell injury is likely through upregulating expression of four Yamanaka transcriptional factors Oct4, Sox2, Klf4 and c-Myc (OSKM in abbreviation). Our studies thus reveal CD47 as a negative regulator in intestinal epithelial cell renewal during colitis through downregulating OSKM transcriptional factors.