Department of Medicine and Ageing Sciences, Gabriele d'Annunzio University of Chieti-Pescara, Chieti, Italy.
Center for Advanced Studies and Technology, Gabriele d'Annunzio University of Chieti-Pescara, Chieti, Italy.
Inflamm Bowel Dis. 2024 Aug 1;30(8):1406-1418. doi: 10.1093/ibd/izae046.
Hypoxia is an essential gastrointestinal (GI) tract phenomenon that influences both physiologic and pathologic states. Hypoxia-inducible factors (HIFs), the primary drivers of cell adaptation to low-oxygen environments, have been identified as critical regulators of gut homeostasis: directly, through the induction of different proteins linked to intestinal barrier stabilization (ie, adherent proteins, tight junctions, mucins, integrins, intestinal trefoil factor, and adenosine); and indirectly, through the regulation of several immune cell types and the modulation of autophagy and inflammatory processes. Furthermore, hypoxia and HIF-related sensing pathways influence the delicate relationship existing between bacteria and mammalian host cells. In turn, gut commensals establish and maintain the physiologic hypoxia of the GI tract and HIF-α expression. Based on this premise, the goals of this review are to (1) highlight hypoxic molecular pathways in the GI tract, both in physiologic and pathophysiologic settings, such as inflammatory bowel disease; and (2) discuss a potential strategy for ameliorating gut-related disorders, by targeting HIF signaling, which can alleviate inflammatory processes, restore autophagy correct mechanisms, and benefit the host-microbiota equilibrium.
缺氧是一种重要的胃肠道（GI）现象，它影响生理和病理状态。缺氧诱导因子（HIFs）是细胞适应低氧环境的主要驱动因素，被认为是肠道内稳态的关键调节剂：直接通过诱导与肠道屏障稳定相关的不同蛋白（例如黏附蛋白、紧密连接、粘蛋白、整合素、肠三叶因子和腺苷）；间接通过调节几种免疫细胞类型和自噬和炎症过程的调节。此外，缺氧和 HIF 相关的感应途径影响细菌和哺乳动物宿主细胞之间存在的微妙关系。反过来，肠道共生菌建立和维持胃肠道的生理性缺氧和 HIF-α表达。基于这一前提，本综述的目的是：（1）强调胃肠道中的缺氧分子途径，包括生理和病理生理环境，如炎症性肠病；（2）讨论通过靶向 HIF 信号改善与肠道相关疾病的潜在策略，这可以减轻炎症过程，恢复自噬正确机制，并有益于宿主-微生物平衡。
