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

Abstract

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.

Potential biomarkers of HCC based on gene expression and DNA methylation profiles

“…The tyrosine kinase inhibitor, genistein, has been demonstrated to induce apoptosis and cell cycle arrest in HepG2 cells by activating the p53 signaling pathway (30). The forkhead box O1 (Foxo) signaling pathway participates in the regulation of multiple biological processes, including cellular responses to oxidative stress, cellular apoptosis and cell proliferation (31)(32)(33). It was reported that juglanthraquinone C could induce the apoptosis of HCC cells by activating the Foxo signaling pathway (34).…”

Effects of the IGF-1/PTEN/Akt/FoxO signaling pathway on male reproduction in rats subjected to water immersion and restraint stress

“…Our previous study demonstrated that FoxO3a and FoxO4 serve major roles in the digestive tract (27,39–41). A previous study regarding the male reproductive system demonstrated that FoxO1 served a key role in initiating spermatogenesis; however, FoxO3a and FoxO4 did not (39).…”

“…Rats received regular rat chow and tap water ad libitum , and were housed individually at 25°C and 65–70% humidity under a 12-h:12-h light/dark cycle. WRS models were established as described in our previous study (27). For each time point, six rats were sacrificed after 0, 3 and 7 h of WRS, whereas others were fed normally 1 h after WRS and six were sacrificed at several time points (4, 8 and 15 days) after the end of 7 h WRS.…”

“…IHC for IGF-1 (1:1,00), PTEN (1:200), total Akt (1:200) and FoxO1 (1:300) was performed on formalin-fixed, paraffin-embedded testicular tissue sections using a standard protocol, as described previously, using DAB and hematoxylin counterstaining (27,31). …”

Comparative proteomic analysis of rats subjected to water immersion and restraint stress as an insight into gastric ulcers

“…WRS can cause several diseases, including acute gastroenteritis, peptic ulcers and colitis ( 3 ). In our previous studies, a gastric ulcer model was successfully established using rats exposed to WRS, providing a solid foundation for the present study ( 4 , 5 ).…”