ArticleThe Journal of biological chemistry2015
PHD3 Stabilizes the Tight Junction Protein Occludin and Protects Intestinal Epithelial Barrier Function.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 65 citations in OpenAlex.
- The effects of drinking water with essential oils-organic acids blend replacing preventive antibiotics during withdrawal period on growth performance and gut health of broilers in a commercial farm.Poultry science · 2026Article
- Intestinal mucosal barrier repair and immune regulation with an AI-developed gut-restricted PHD inhibitor.Nature biotechnology · 2025Article
- Intestinal Epithelial Tight Junction Barrier Regulation by Novel Pathways.Inflammatory bowel diseases · 2025Review
- Heat stress in poultry: the role of nutritional supplements in alleviating heat stress and enhancing gut health in poultry.Frontiers in veterinary science · 2025Review
- Collagen prolyl 4-hydroxylase subunit α member-induced head and neck squamous cell carcinoma aggressiveness is antagonized by LLGL2 via reduced expression of occludin.Acta biochimica et biophysica Sinica · 2024Article
- PHD1-3 oxygen sensors in vivo-lessons learned from gene deletions.Pflugers Archiv : European journal of physiology · 2024Review
- Analysis of fecal microbiota and related clinical indicators in ICU patients with sepsis.Heliyon · 2024Article
- Hypoxia-Induced Signaling in Gut and Liver Pathobiology.Annual review of pathology · 2024Review
- PHD3 inhibits colon cancer cell metastasis through the occludin-p38 pathway.Acta biochimica et biophysica Sinica · 2023Article
- Mechanism of Acupuncture and Moxibustion on Promoting Mucosal Healing in Ulcerative Colitis.Chinese journal of integrative medicine · 2023Review
- Hypoxia in the Pathophysiology of Inflammatory Bowel Disease.Comprehensive Physiology · 2023Article
- Proline hydroxylation of CREB-regulated transcriptional coactivator 2 controls hepatic glucose metabolism.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Autophagy Reduces the Degradation and Promotes Membrane Localization of Occludin to Enhance the Intestinal Epithelial Tight Junction Barrier against Paracellular Macromolecule Flux.Journal of Crohn's & colitis · 2023Article
- Article
- Hypoxia and Intestinal Inflammation: Common Molecular Mechanisms and Signaling Pathways.International journal of molecular sciences · 2023Review
- Hypoxia inducible factor prolyl hydroxylases in inflammatory bowel disease.Frontiers in pharmacology · 2023Review
- Redox and Metabolic Regulation of Intestinal Barrier Function and Associated Disorders.International journal of molecular sciences · 2022Review
- PHD3 inhibits cell proliferation through hydroxylation of PAX2 at proline 9.Acta biochimica et biophysica Sinica · 2022Article
- Human Fecal Microbiota Transplantation Reduces the Susceptibility to Dextran Sulfate Sodium-Induced Germ-Free Mouse Colitis.Frontiers in immunology · 2022Article
- Oxygen-sensing mechanisms in development and tissue repair.Development (Cambridge, England) · 2021Review
Corrections and comments
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Authors and funding
13 authors at 7 institutions in 2 countries.
Funding
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.