ArticleProceedings of the National Academy of Sciences of the United States of America2013
Control of creatine metabolism by HIF is an endogenous mechanism of barrier regulation in colitis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 150 citations in OpenAlex.
- Metabolic host-microbe crosstalk in stabilization of epithelial HIF.Microbiome · 2026Article
- Integrative profiling of gut microbiome, bacteriophagenome, and predicted metabolome in obese adults: novel insights into intervention targets.BMC microbiology · 2026Article
- From mechanisms to therapeutics: molecular insights into gastrointestinal injury under high-altitude hypoxia.Frontiers in microbiology · 2026Review
- Modifying microbially derived short chain fatty acids to promote health.The Journal of physiology · 2026Review
- Creatine kinase B, a downstream effector of c-Myb, controls migration of osteosarcoma cells via regulation of N-cadherin.Cancer cell international · 2025Article
- The gut-kidney axis in high-altitude hypoxia: pathophysiological mechanisms and the central role of hypoxia inducible factor.Annals of medicine · 2025Review
- Epstein-Barr virus-transformed B-cells from a hypoxia model of the germinal center requires external unsaturated fatty acids.PLoS pathogens · 2025Article
- Hypoxia and Multilineage Communication in 3D Organoids for Human Disease Modeling.Biomimetics (Basel, Switzerland) · 2025Review
- Orchestration of Gut-Liver-Associated Transcription Factors in MAFLD: From Cross-Organ Interactions to Therapeutic Innovation.Biomedicines · 2025Review
- Optimizing Poultry Growth and Meat Quality: Effects of Guanidinoacetic Acid Supplementation in Yellow-Feathered Broilers.Veterinary sciences · 2025Article
- CKMT1 deficiency contributes to mitochondrial dysfunction and promotes intestinal epithelial cell apoptosis via reverse electron transfer-derived ROS in colitis.Cell death & disease · 2025Article
- Spatial mapping of dextran sodium sulphate-induced intestinal inflammation and its systemic effects.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Physiologic hypoxia in the intestinal mucosa: a central role for short-chain fatty acids.American journal of physiology. Cell physiology · 2024Review
- A covalent creatine kinase inhibitor ablates glioblastoma migration and sensitizes tumors to oxidative stress.Scientific reports · 2024Article
- HIF-2α-dependent induction of miR-29a restrains TNature communications · 2024Article
- Colonic epithelial hypoxia remains constant during the progression of diabetes in male UC Davis type 2 diabetes mellitus rats.BMJ open diabetes research & care · 2024Article
- Research Progress on the Mechanism of Intestinal Barrier Damage and Drug Therapy in a High Altitude Environment.Current drug delivery · 2024Review
- Crosstalk between hypoxia-inducible factor-1α and short-chain fatty acids in inflammatory bowel disease: key clues toward unraveling the mystery.Frontiers in immunology · 2024Review
- Disruption of hypoxia-inducible factor-2α in neutrophils decreases colitis-associated colon cancer.American journal of physiology. Gastrointestinal and liver physiology · 2024Article
- Fundamental role for the creatine kinase pathway in protection from murine colitis.Mucosal immunology · 2023Article
28 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
Mucosal surfaces of the lower gastrointestinal tract are subject to frequent, pronounced fluctuations in oxygen tension, particularly during inflammation. Adaptive responses to hypoxia are orchestrated largely by the hypoxia-inducible transcription factors (HIFs). As HIF-1α and HIF-2α are coexpressed in mucosal epithelia that constitute the barrier between the lumen and the underlying immune milieu, we sought to define the discrete contribution of HIF-1 and HIF-2 transactivation pathways to intestinal epithelial cell homeostasis. The present study identifies creatine kinases (CKs), key metabolic enzymes for rapid ATP generation via the phosphocreatine-creatine kinase (PCr/CK) system, as a unique gene family that is coordinately regulated by HIF. Cytosolic CKs are expressed in a HIF-2-dependent manner in vitro and localize to apical intestinal epithelial cell adherens junctions, where they are critical for junction assembly and epithelial integrity. Supplementation with dietary creatine markedly ameliorated both disease severity and inflammatory responses in colitis models. Further, enzymes of the PCr/CK metabolic shuttle demonstrate dysregulated mucosal expression in a subset of ulcerative colitis and Crohn disease patients. These findings establish a role for HIF-regulated CK in epithelial homeostasis and reveal a fundamental link between cellular bioenergetics and mucosal barrier.
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