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Abnormal differentiation of intestinal epithelium and intestinal barrier dysfunction in diabetic mice associated with depressed Notch/NICD transduction in Notch/Hes1 signal pathway

机译:腹菌小鼠肠道上皮和肠道阻隔功能障碍的异常分化与凹陷/ HES1信号通路中抑制肠/ NICD转导相关的糖尿病小鼠

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摘要

Proliferative change and intestinal barrier dysfunction in intestinal mucosa of diabetes have been described, but the differentiation characteristics of intestinal epithelial cells (IECs) and the mechanisms in the IECs development remain unclear. To explore the intestinal epithelial constitution patterns and barrier function, the diabetic mouse model was induced by streptozotocin. Tight junctions between IECs were significantly damaged and the serum level of D-lactate was raised in diabetic mice (P < 0.05). The expression of Zo1 and Ocln in the small intestine of diabetic mice were lower, while the markers for absorptive cell (SI) and Paneth cell (Lyz1) were significantly higher than in control mice (P < 0.05). The expression of Msi1, Notch1, and Dll1 in small intestine gradually increased throughout the course of hyperglycemia in diabetic mice (P < 0.05). However, the expression of NICD, RBP-jk, Math1, and Hes1 had a reverse trend compared with Msil and Notchl. Intestinal absorptive cells and Paneth cells had a high proliferation rate in diabetic mice. However, the intestinal barrier dysfunction associated with the decreased expressions of Zol and Ocln was detected throughout hyperglycemia. In conclusion, downregulation of Notch/Hes1 signal pathway caused by depressed Notch/NICD transduction is associated with the abnormal differentiation of IECs and intestinal barrier dysfunction in diabetic mice.
机译:已经描述了患有胎面粘膜粘膜的增殖变化和肠道阻隔功能障碍,但肠上皮细胞(IECS)的分化特性及其IECS发展中的机制仍然尚不清楚。为了探索肠上皮结构模式和屏障功能,通过链脲佐菌素诱导糖尿病小鼠模型。 IECs之间的紧张连接受到显着损害,糖尿病小鼠饲养D-乳酸血清水平(P <0.05)。 ZO1和OCLN在糖尿病小鼠的小肠中的表达较低,而吸收细胞(Si)和Paneth细胞(LyZ1)的标志物显着高于对照小鼠(P <0.05)。在糖尿病小鼠的高血糖血症过程中,MSI1,Notch1和DLL1的表达逐渐增加(P <0.05)。然而,与MSIL和Notchl相比,NICD,RBP-JK,MATH1和HES1的表达具有反向趋势。肠吸收细胞和甘露体细胞在糖尿病小鼠中具有高增殖率。然而,在高血糖症中检测到与ZOL和OCLN表达的表达相关的肠道屏障功能障碍。总之,由抑郁的凹口/ NICD转导引起的Notch / Hes1信号途径的下调与糖尿病小鼠IECs和肠道阻隔功能障碍的异常分化有关。

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