Effect of the IGF-1/PTEN/Akt/FoxO signaling pathway on the development             and healing of water immersion and restraint stress-induced gastric ulcers in             rats.
Insulin-like growth factor 1 (IGF-1) and Akt [also known as protein kinase B (PKB)] proteins have been reported to exhibit gastroprotective effects by reducing water immersion and restraint stress (WRS)-induced gastric mucosal cellular apoptosis. To confirm whether the IGF-1/PTEN/Akt/FoxO signaling pathway is effective in protecting against gastric ulcers, our current study was conducted to examine the expression and localization of IGF-1, phosphatase and tensin homologue deleted on chromosome 10 (PTEN), Akt and O subfamily of forkhead box (FoxO) proteins, caspase-3 activity and the number of apoptotic cells in gastric mucosa of rats subjected to WRS. Our results demonstrated that WRS induced gastric ulcers by enhancing cell apoptosis in rat gastric mucosa. In addition, in normal rat gastric mucosa, PTEN, total Akt and FoxO1 were found mainly in the cell cytoplasm of fundic glands in the lamina propria close to the muscularis mucosa. In addition, strong staining of IGF-1, FoxO3a and FoxO4 in the gastric mucosa was primarily concentrated in the cell cytoplasm of the fundic glands in whole lamina propria. However, in rat gastric ulcers, IGF-1, total Akt, FoxO3a and FoxO4 were localized in proximity to the base of the ulcer margin and were also present in the granulation tissues of the gastric ulcers. Moreover, in the rat gastric ulcers, the mRNA transcript levels of IGF-1, PTEN, Akt-1, Akt-2, FoxO3 and FoxO4 were upregulated in the gastric ulcer margin, with a peak between Days 4 and 8 following 7 h of WRS. In conclusion, our results imply that the IGF-1/PTEN/Akt/FoxO signaling pathway plays a certain role(s) in the protection against ulceration through the regulation of cellular apoptosis as observed in the development and healing of rat gastric ulcers.
College of Animal Science and Technology, Nanjing Agricultural                     University, Nanjing 210095, P.R. China.
Pan
P
Huang
Zhengrong
Z
Zhou
Hao
H
Wang
Quanwei
Q
Wei
Liang
L
Zhang
Xin
X
Zhou
Reinhold J
RJ
Hutz
Fangxiong
F
Shi
D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D021381:Protein Transport; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013276:Stomach Ulcer / Q000209:etiology / Q000378:metabolism*; D013312:Stress, Physiological; D014945:Wound Healing
D051858:Forkhead Transcription Factors; D007334:Insulin-Like Growth Factor I; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase