PHD3 Stabilizes the Tight Junction Protein Occludin and Protects Intestinal Epithelial Barrier Function
文献类型：期刊论文
| 作者 | Chen, Ying; Zhang, Hai-Sheng; Fong, Guo-Hua; Xi, Qiu-Lei; Wu, Guo-Hao; Bai, Chen-Guang; Ling, Zhi-Qiang; Fan, li（范莉）; Xu, Yi-Ming; Qin, Yan-Qing |
| 刊名 | JOURNAL OF BIOLOGICAL CHEMISTRY
 |
| 出版日期 | 2015 |
| 卷号 | 290期号:33页码:20580-20589 |
| 通讯作者 | Fang, J (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Lab Food Safety Res, Shanghai 200031, Peoples R China. |
| 英文摘要 | Prolyl hydroxylase domain proteins (PHDs) control cellular adaptation to hypoxia. PHDs are found involved in inflammatory bowel disease (IBD); however, the exact role of PHD3, a member of the PHD family, in IBD remains unknown. We show here that PHD3 plays a critical role in maintaining intestinal epithelial barrier function. We found that genetic ablation of Phd3 in intestinal epithelial cells led to spontaneous colitis in mice. Deletion of PHD3 decreases the level of tight junction protein occludin, leading to a failure of intestinal epithelial barrier function. Further studies indicate that PHD3 stabilizes occludin by preventing the interaction between the E3 ligase Itch and occludin, in a hydroxylase-independent manner. Examination of biopsy of human ulcerative colitis patients indicates that PHD3 is decreased with disease severity, indicating that PHD3 down-regulation is associated with progression of this disease. We show that PHD3 protects intestinal epithelial barrier function and reveal a hydroxylase-independent function of PHD3 in stabilizing occludin. These findings may help open avenues for developing a therapeutic strategy for IBD. |
| 类目[WOS] | Biochemistry & Molecular Biology |
| 研究领域[WOS] | Biochemistry & Molecular Biology |
| 关键词[WOS] | HYPOXIA-INDUCIBLE-FACTOR ; PROLYL HYDROXYLASE INHIBITION ; INFLAMMATORY-BOWEL-DISEASE ; NF-KAPPA-B ; EXPERIMENTAL COLITIS ; OXYGEN SENSOR ; DOMAIN ; EGLN3 ; HIF ; MICE |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000359608900053 |
| 公开日期 | 2015-12-24 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/327]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所_营养与癌症研究组 |
| 推荐引用方式 GB/T 7714 | Chen, Ying,Zhang, Hai-Sheng,Fong, Guo-Hua,et al. PHD3 Stabilizes the Tight Junction Protein Occludin and Protects Intestinal Epithelial Barrier Function[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2015,290(33):20580-20589. |
| APA | Chen, Ying.,Zhang, Hai-Sheng.,Fong, Guo-Hua.,Xi, Qiu-Lei.,Wu, Guo-Hao.,...&Fang, Jing.(2015).PHD3 Stabilizes the Tight Junction Protein Occludin and Protects Intestinal Epithelial Barrier Function.JOURNAL OF BIOLOGICAL CHEMISTRY,290(33),20580-20589. |
| MLA | Chen, Ying,et al."PHD3 Stabilizes the Tight Junction Protein Occludin and Protects Intestinal Epithelial Barrier Function".JOURNAL OF BIOLOGICAL CHEMISTRY 290.33(2015):20580-20589. |
入库方式： OAI收割
来源：上海营养与健康研究所
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