Lun Jie, Zhang Hongwei, Guo Jing, Yu Mengchao, Fang Jing
Department of Oncology, Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao, China.
Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, China.
Front Pharmacol. 2023 May 2;14:1045997. doi: 10.3389/fphar.2023.1045997. eCollection 2023.
Inflammatory bowel disease (IBD) is a chronic disease that is characterized by intestinal inflammation. Epithelial damage and loss of intestinal barrier function are believed to be the hallmark pathologies of the disease. In IBD, the resident and infiltrating immune cells consume much oxygen, rendering the inflamed intestinal mucosa hypoxic. In hypoxia, the hypoxia-inducible factor (HIF) is induced to cope with the lack of oxygen and protect intestinal barrier. Protein stability of HIF is tightly controlled by prolyl hydroxylases (PHDs). Stabilization of HIF through inhibition of PHDs is appearing as a new strategy of IBD treatment. Studies have shown that PHD-targeting is beneficial to the treatment of IBD. In this Review, we summarize the current understanding of the role of HIF and PHDs in IBD and discuss the therapeutic potential of targeting PHD-HIF pathway for IBD treatment.
炎症性肠病（IBD）是一种以肠道炎症为特征的慢性疾病。上皮损伤和肠道屏障功能丧失被认为是该疾病的标志性病理特征。在IBD中，常驻和浸润的免疫细胞消耗大量氧气，导致炎症性肠黏膜缺氧。在缺氧状态下，缺氧诱导因子（HIF）被诱导以应对缺氧并保护肠道屏障。HIF的蛋白质稳定性受到脯氨酰羟化酶（PHD）的严格控制。通过抑制PHD来稳定HIF正成为IBD治疗的一种新策略。研究表明，靶向PHD对IBD治疗有益。在本综述中，我们总结了目前对HIF和PHD在IBD中的作用的理解，并讨论了靶向PHD-HIF通路用于IBD治疗的潜在治疗价值。
