PHD3 Stabilizes the Tight Junction Protein Occludin and Protects Intestinal Epithelial Barrier Function

• DOI: 10.1074/jbc.m115.653584
• Publication Date: 2015-06-30T02:14:44Z
• Authors: Ying Chen; Hai-Sheng Zhang; Guo-Hua Fong; Qiu-Lei Xi; Guo-Hao Wu; Chen-Guang Bai; Zhi-Qiang Ling; Li Fan; Yi-Ming Xu; Yan-Qing Qin; Tang-Long Yuan; Heng Sun; Jing Fang
• Keywords: Occludin; Barrier function; Intestinal mucosa; Claudin; Hypoxia; Intestinal epithelium

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 PHD family, IBD remains unknown. We show here that PHD3 plays critical maintaining intestinal epithelial barrier function. genetic ablation Phd3 cells led spontaneous colitis mice. Deletion decreases level tight junction protein occludin, leading failure Further studies indicate stabilizes occludin by preventing interaction between E3 ligase Itch and hydroxylase-independent manner. Examination biopsy human ulcerative patients indicates is decreased with severity, indicating down-regulation associated progression this disease. protects function reveal stabilizing occludin. These findings may help open avenues for developing therapeutic strategy IBD.