Oxygen (O2) is essential for cellular metabolism and biochemical reactions. When the demand for O2 exceeds the supply, hypoxia occurs. Hypoxia-inducible factors (HIFs) are essential to activate adaptive and survival responses following hypoxic stress. In the gut (intestines) and liver, the presence of oxygen gradients or physiologic hypoxia is necessary to maintain normal homeostasis. While physiologic hypoxia is beneficial and aids in normal functions, pathological hypoxia is harmful as it exacerbates inflammatory responses and tissue dysfunction and is a hallmark of many cancers. In this review, we discuss the role of gut and liver hypoxia-induced signaling, primarily focusing on HIFs, in the physiology and pathobiology of gut and liver diseases. Additionally, we examine the function of HIFs in various cell types during gut and liver diseases, beyond intestinal epithelial and hepatocyte HIFs. This review highlights the importance of understanding hypoxia-induced signaling in the pathogenesis of gut and liver diseases and emphasizes the potential of HIFs as therapeutic targets.

中文翻译：

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肠道和肝脏病理生物学中缺氧诱导的信号传导


氧气 （O2） 对细胞代谢和生化反应至关重要。当对 O2 的需求超过供应时，就会发生缺氧。缺氧诱导因子 （HIF） 对于激活低氧应激后的适应性和生存反应至关重要。在肠道（肠道）和肝脏中，氧梯度或生理性缺氧的存在对于维持正常的体内平衡是必要的。虽然生理性缺氧是有益的并有助于正常功能，但病理性缺氧是有害的，因为它会加剧炎症反应和组织功能障碍，并且是许多癌症的标志。在这篇综述中，我们讨论了肠道和肝脏缺氧诱导的信号传导在肠道和肝脏疾病的生理学和病理生物学中的作用，主要集中在 HIFs。此外，我们还检查了 HIF 在肠道和肝脏疾病期间各种细胞类型中的功能，超越了肠上皮和肝细胞 HIF。本综述强调了了解缺氧诱导的信号转导在肠道和肝脏疾病发病机制中的重要性，并强调了 HIFs 作为治疗靶点的潜力。