2014
DOI: 10.1126/scitranslmed.3008523
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PHD Inhibition Mitigates and Protects Against Radiation-Induced Gastrointestinal Toxicity via HIF2

Abstract: Radiation-induced gastrointestinal (GI) toxicity can be a major source of morbidity and mortality after radiation exposure. There is an unmet need for effective preventative or mitigative treatments against the potentially fatal diarrhea and water loss induced by radiation damage to the GI tract. We report that prolyl hydroxylase inhibition by genetic knockout or pharmacologic inhibition of all PHD isoforms by the small molecule dimethyloxyallylglycine (DMOG) increases HIF expression, improves epithelial integ… Show more

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Cited by 122 publications
(135 citation statements)
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“…When the small molecule DMOG was used in combination with irradiation, HIF-1α and HIF-2α stabilization in the GI tract was significantly increased following DMOG and irradiation compared to irradiation alone (27). Interestingly, GI tract-specific genetic knockdown of all three PHDs was necessary for abundant HIF expression, while knockdown of individual PHDs had minimal effects.…”
Section: Phd Inhibition and Epithelial Integrity In Radiotherapymentioning
confidence: 98%
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“…When the small molecule DMOG was used in combination with irradiation, HIF-1α and HIF-2α stabilization in the GI tract was significantly increased following DMOG and irradiation compared to irradiation alone (27). Interestingly, GI tract-specific genetic knockdown of all three PHDs was necessary for abundant HIF expression, while knockdown of individual PHDs had minimal effects.…”
Section: Phd Inhibition and Epithelial Integrity In Radiotherapymentioning
confidence: 98%
“…The effects of irradiation alone on HIF stabilization in normal tissues appear complex, with HIF-1α and HIF-2α being detected in the colon, liver, and kidneys, but not in other organs such as the lung following irradiation (27). When the small molecule DMOG was used in combination with irradiation, HIF-1α and HIF-2α stabilization in the GI tract was significantly increased following DMOG and irradiation compared to irradiation alone (27).…”
Section: Phd Inhibition and Epithelial Integrity In Radiotherapymentioning
confidence: 99%
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