Fortunellin-Induced Modulation of Phosphatase and Tensin Homolog by MicroRNA-374a Decreases Inflammation and Maintains Intestinal Barrier Function in Colitis.

Abstract	Activation of phosphatase and tensin homolog (PTEN) is known to induce cell apoptosis. MicroRNA-374a (miR-374a), which can suppress PTEN expression, has been found abnormally expressed in inflammatory bowel disease (IBD). Fortunellin is a citrus flavonoid that is a potential anti-inflammation agent in inflammatory diseases. The present study investigated the effects and mechanisms underlying fortunellin-induced inhibition of PTEN in IBD. Colitis was established in rats by the intracolonic administration of 2,4,6-trinitrobenzene sulfonic acid to mimic human ulcerative colitis, which is the main type of IBD. miR-374a expression was measured by quantitative real-time polymerase chain reaction, and the regulation of PTEN by miR-374a was evaluated by dual luciferase reporter assay. Western blotting was used to measure the corresponding protein expression. Fortunellin ameliorated colitis symptoms, including excessive inflammation and oxidative stress. Fortunellin decreased epithelial cell apoptosis through inhibiting PTEN expression in colitis. Fortunellin-induced downregulation of PTEN could be counteracted by miR-374a depletion. Moreover, knockdown of miR-374a in vivo partly inhibited the effects of fortunellin on rat colitis. In conclusion, PTEN inhibition contributes to the amelioration effects of fortunellin on colitis. It was confirmed that fortunellin targets miR-374a, which is a negative regulator of PTEN. This study provides novel insights into the pathological mechanisms and treatment alternatives of colitis.
Authors	Yongjian Xiong, Juanjuan Qiu, Changyi Li, Yang Qiu, Li Guo, Yuejian Liu, Jiajia Wan, Yuchun Li, Guokai Wu, Liang Wang, Zijuan Zhou, Jianyi Dong, Chunhua Du, Dapeng Chen, Huishu Guo
Journal	Frontiers in immunology (Front Immunol) Vol. 9 Pg. 83 ( 2018) ISSN: 1664-3224 [Print] Switzerland
PMID	29472916 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Antagomirs Flavonoids Glycosides MicroRNAs Reactive Oxygen Species fortunellin PTEN Phosphohydrolase
Topics	Animals Antagomirs (genetics) Apoptosis (drug effects, genetics) Biopsy Cell Membrane Permeability Colitis (etiology, metabolism, pathology) Disease Models, Animal Flavonoids (adverse effects, pharmacology) Gene Expression Regulation Glycosides (adverse effects, pharmacology) Intestinal Mucosa (metabolism, pathology) Male MicroRNAs (genetics) Oxidative Stress PTEN Phosphohydrolase (genetics) RNA Interference Rats Reactive Oxygen Species (metabolism) Symptom Assessment

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