Hai-Yi Zhang, Ya-Qing Shu, Yan Li, Ya-Lin Hu, Zhi-Hong Wu, Zhi-Peng Li, Yao Deng, Zi-Jian Zheng, Xiao-Jing Zhang, Liu-Fei Gong, Yang Luo, Xiao-Yu Wang, Hong-Ping Li, Xiao-Ping Liao, Gong Li, Hao Ren, Wei Qiu, Jian Sun
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Abstract
Sleep deprivation (SD) has been reported to induce intestinal damage by several mechanisms, yet its role in modulating epithelial repair remains unclear. In this study, we find that chronic SD leads to colonic damage through continuous hypoxia. However, HIF1α, which generally responds to hypoxia to modulate barrier integrity, was paradoxically dysregulated in the colon. Further investigation revealed that a metabolic disruption during SD causes accumulation of α-ketoglutarate in the colon. The excessive α-ketoglutarate degrades HIF1α protein through PHD2 (prolyl hydroxylase 2) to abolish the intestinal repair functions of HIF1α. Collectively, these findings provide insights into how SD can exacerbate intestinal damage by fine-tuning metabolism to abolish HIF1α-mediated repair.
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Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted.
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