Elevated expression of forkhead box protein O1 (FoxO1) in alcohol-induced intestinal barrier dysfunction.
Alcohol-induced intestinal barrier dysfunction is a major contributor to alcoholic liver disease (ALD). Forkhead box protein O1 (FoxO1) is a member of the mammalian forkhead box O class (FoxO) subfamily that regulates a wide array of cellular processes. In the present study, we used both an alcohol-fed mouse model and an alcohol-treated Caco-2 intestinal epithelial cell monolayer in vitro model to investigate whether FoxO1 is involved in alcohol-induced intestinal barrier dysfunction. We found that chronic alcohol exposure to mice significantly increased both mRNA and protein levels of FoxO1 in all the examined intestinal segments with the most remarkable changes in the ileum. Alcohol treatment increased mRNA and protein levels of FoxO1 and promoted nuclear translocation of FoxO1 in Caco-2 cells. Furthermore, alcohol treatment with Caco-2 cells resulted in a significant decrease in the epithelial transepithelial electrical resistance (TEER) value, which was attenuated by knockdown of FoxO1 expression. In conclusion, our data suggest that activation of FoxO1 is likely to be a novel mechanism contributing to the deleterious effects of alcohol on intestinal barrier function.
Department of Gastroenterology, The First Affiliated Hospital of China Medical University, Shenyang 110001, People's Republic of China.
Ying
Y
Wang
Jing
J
Tong
Dawei
D
Zou
Bing
B
Chang
Baifang
B
Wang
Bingyuan
B
Wang
D000818:Animals; D018938:Caco-2 Cells; D004195:Disease Models, Animal; D017097:Electric Impedance; D000431:Ethanol / Q000633:toxicity; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection
D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000431:Ethanol
Alcohol; Caco-2; Forkhead box protein O1 (FoxO1); Intestinal barrier dysfunction; Mice