Huang P, Zhou Z R, Zheng M Q, Shi F X
Laboratory of Animal Reproduction, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China.
Genet Mol Res. 2012 Sep 19;11(4):4775-88. doi: 10.4238/2012.September.19.2.
The insulin growth factor 1/phosphatase and tensin homologue deleted on chromosome 10/Akt/forkhead box (IGF-1/PTEN/Akt/FoxO) signaling pathway reportedly exhibits gastroprotective effects by reducing water immersion and restraint stress (WRS)-induced gastric mucosal cell apoptosis. We examined the expression and localization of IGF-1, PTEN, Akt, and FoxO proteins, caspase-3 activity, and the number of apoptotic cells in the duodenal mucosa of rats subjected to WRS to confirm whether the IGF-1/PTEN/Akt/FoxO signaling pathway has a role in the duodenal mucosa. The results indicated that WRS enhanced cell apoptosis in the duodenal mucosa. In addition, in normal rats, PTEN was found mainly in the cellular cytoplasm of the duodenal glands and lamina propria of villi. IGF-1 and total Akt were observed in the cellular cytoplasm of the duodenal glands. In addition, total Akt was found in the cellular cytoplasm of the myenteric plexus. FoxO3a and FoxO4 were primarily concentrated in the cellular cytoplasm of the lamina propria. Specifically, PTEN, FoxO3a and FoxO4 were also localized in the cellular cytoplasm of lamina propria of restituted villi in the duodenal mucosa of rat subjected to WRS. In addition, messenger RNA transcript levels of IGF-1, PTEN, Akt1, Akt2, FoxO3, and FoxO4 were upregulated in the duodenal mucosa, with a peak between the 4th and 8th day after 7 h of WRS. Furthermore, the results also suggested that Akt3 messenger RNA transcript levels in the duodenal mucosa of rats after WRS showed no significant differences compared with those in the non-WRS group. Collectively, our results implied that the IGF-1/ PTEN/Akt/FoxO signaling pathway was effective in regulating cellular apoptosis in the duodenal mucosa of rats after WRS.
据报道，胰岛素生长因子1/第10号染色体上缺失的磷酸酶和张力蛋白同源物/蛋白激酶B/叉头框（IGF-1/PTEN/Akt/FoxO）信号通路通过减少水浸束缚应激（WRS）诱导的胃黏膜细胞凋亡发挥胃保护作用。我们检测了WRS处理大鼠十二指肠黏膜中IGF-1、PTEN、Akt和FoxO蛋白的表达及定位、半胱天冬酶-3活性和凋亡细胞数量，以确定IGF-1/PTEN/Akt/FoxO信号通路在十二指肠黏膜中是否起作用。结果表明，WRS增强了十二指肠黏膜中的细胞凋亡。此外，在正常大鼠中，PTEN主要存在于十二指肠腺和绒毛固有层的细胞质中。在十二指肠腺的细胞质中观察到IGF-1和总Akt。此外，在肌间神经丛的细胞质中发现了总Akt。FoxO3a和FoxO4主要集中在固有层的细胞质中。具体而言，在经受WRS的大鼠十二指肠黏膜中，修复绒毛固有层的细胞质中也定位有PTEN、FoxO3a和FoxO4。此外，十二指肠黏膜中IGF-1、PTEN、Akt1、Akt2、FoxO3和FoxO4的信使核糖核酸转录水平上调，在WRS 7小时后的第4天至第8天达到峰值。此外，结果还表明，WRS后大鼠十二指肠黏膜中Akt3信使核糖核酸转录水平与非WRS组相比无显著差异。总体而言，我们的结果表明，IGF-1/PTEN/Akt/FoxO信号通路在调节WRS后大鼠十二指肠黏膜中的细胞凋亡方面有效。
