| Autor: |
Zhi-Wei, Dong, Hui, Liu, Fei-Fei, Su, Xiao-Zhou, Fan, Yong, Zhang, Peng, Liu |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
World journal of gastroenterology. 28(9) |
| ISSN: |
2219-2840 |
| Popis: |
Intestinal ischemia/reperfusion (I/R) injury is a fatal syndrome that occurs under many clinical scenarios. The apoptosis of intestinal cells caused by ischemia can cause cell damage and provoke systemic dysfunction during reperfusion. However, the mechanism of I/R-induced apoptosis remains unclear. Cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-activated chloride channel. Few researchers have paid attention to its role in intestinal I/R injury, or the relationship between CFTR and intestinal apoptosis induced by hypoxia/reoxygenation (H/R).To investigate the effects of CFTR on I/R-induced intestinal apoptosis and its underlying molecular mechanisms.An intestinal I/R injury model was established in mice with superior mesenteric artery occlusion, and Caco2 cells were subjected to H/R for the simulation of I/RThe results suggested that CFTR overexpression significantly increased the Caco2 cell viability and decreased cell apoptosis induced by the H/R. Interestingly, we found that the translocation of p65, an NF-κB member, from the cytoplasm to the nucleus after H/R treatment can be reversed by the overexpression of CFTR, the NF-κB P65 would return from the nucleus to the cytoplasm as determined by immunostaining. We also discovered that CFTR inhibited cell apoptosis in the H/R-treated cells, and this effect was significantly curbed by the NF-κB activator BA, AKT inhibitor GSK690693 and the PI3K inhibitor LY294002. Moreover, we demonstrated that CFTR overexpression could reverse the decreased PI3K/AKT expression induced by the I/R treatmentThe results of the present study indicate that the overexpression of CFTR protects Caco2 cells from H/R-induced apoptosis; furthermore, it also inhibits H/R-induced apoptosis through the PI3K/AKT/NF-κB signaling pathway in H/R-treated Caco2 cells and intestinal tissues. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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