Effect  of the IGF-1/PTEN/Akt/FoxO signaling pathway in the duodenal mucosa of rats  subjected to water immersion and restraint stress.
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.
Laboratory of Animal Reproduction, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China.
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P
Huang
Z R
ZR
Zhou
M Q
MQ
Zheng
F X
FX
Shi
D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004386:Duodenum / Q000378:metabolism* / Q000473:pathology; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D005786:Gene Expression Regulation; D007101:Immersion; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008871:Microvilli / Q000378:metabolism; D009928:Organ Specificity; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D015398:Signal Transduction; D013315:Stress, Psychological / Q000378:metabolism
C499515:FOXO3 protein, rat; C524737:FOXO4 protein, rat; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C487216:Pten protein, rat; C505410:Casp3 protein, rat; D053148:Caspase 3