Department of Gastroenterology, The Second Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
Pathol Res Pract. 2018 Feb;214(2):245-252. doi: 10.1016/j.prp.2017.11.004. Epub 2017 Nov 8.
Apoptosis in intestinal epithelial cells (IECs) prevents the development of Crohn's disease (CD), a type of inflammatory bowel disease (IBD). Runt-related transcription factor 2 (Runx2) inhibits apoptosis in osteosarcoma-derived U2OS cells via down-regulating the transcriptional activity of p53. However, the expression and function of Runx2 in CD remain unclear. In this study, Runx2 protein levels were decreased in the intestinal epithelial cells (IECs) of CD patients and in a mouse 2, 4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis model; in contrast, the expression levels of p53 and Bax, a p53-target gene, were increased. In a TNF-α-treated HT29 cell colitis model, the down-regulation of Runx2 was accompanied by the up-regulation of apoptotic markers, including cleaved caspase-3 and Bax. Furthermore, Runx2 overexpression effectively decreased TNF-α-induced Bax and cleaved caspase-3 expression levels. In conclusion, our data indicated that Runx2 might protect IECs from apoptosis in CD, thus revealing a novel molecular target for treating CD.
肠上皮细胞 (IECs) 的凋亡可预防克罗恩病 (CD) 的发生,CD 是一种炎症性肠病 (IBD)。 runt 相关转录因子 2 (Runx2) 通过下调 p53 的转录活性抑制骨肉瘤衍生的 U2OS 细胞中的凋亡。然而,Runx2 在 CD 中的表达和功能仍不清楚。在本研究中,CD 患者和 2,4,6-三硝基苯磺酸 (TNBS) 诱导的结肠炎模型的肠上皮细胞 (IECs) 中 Runx2 蛋白水平降低;相比之下,p53 和 Bax(p53 靶基因)的表达水平增加。在 TNF-α 处理的 HT29 细胞结肠炎模型中,Runx2 的下调伴随着凋亡标志物的上调,包括 cleaved caspase-3 和 Bax。此外,Runx2 的过表达有效降低了 TNF-α 诱导的 Bax 和 cleaved caspase-3 表达水平。总之,我们的数据表明 Runx2 可能保护 IECs 免受 CD 中的细胞凋亡,从而为治疗 CD 提供了一个新的分子靶点。