Qiu Bingquan, Yuan Piaoliu, Du Xiaojuan, Jin Hongfang, Du Junbao, Huang Yaqian
Department of Pediatrics, Peking University First Hospital, Beijing, 100034, China.
State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, 100191, China.
Heliyon. 2023 Jun 9;9(6):e17167. doi: 10.1016/j.heliyon.2023.e17167. eCollection 2023 Jun.
Hypoxia-inducible factor-1 (HIF-1), a heterodimeric transcription factor composed of the α and β subunits, regulates cellular adaptive responses to hypoxia. Macrophages, which are derived from monocytes, function as antigen-presenting cells that activate various immune responses. HIF-1α regulates the immune response, viability, migration, phenotypic plasticity, and metabolism of macrophages. Specifically, macrophage-derived HIF-1α can prevent excessive pro-inflammatory responses by attenuating the transcriptional activity of nuclear factor-kappa B and . HIF-1α modulates macrophage migration by inducing the release of various chemokines and providing necessary energy. HIF-1α promotes macrophage M1 polarization by targeting glucose metabolism. Additionally, HIF-1α induces the upregulation of glycolysis-related enzymes and intermediates of the tricarboxylic acid cycle and pentose phosphate pathway. HIF-1α promotes macrophage apoptosis, necroptosis and reduces autophagy. The current review highlights the mechanisms associated with the regulation of HIF-1α stabilization in macrophages as well as the role of HIF-1α in modulating the physiological functions of macrophages.
缺氧诱导因子-1（HIF-1）是一种由α和β亚基组成的异二聚体转录因子，可调节细胞对缺氧的适应性反应。巨噬细胞来源于单核细胞，作为抗原呈递细胞发挥作用，激活各种免疫反应。HIF-1α调节巨噬细胞的免疫反应、活力、迁移、表型可塑性和代谢。具体而言，巨噬细胞衍生的HIF-1α可通过减弱核因子-κB的转录活性来预防过度的促炎反应。HIF-1α通过诱导各种趋化因子的释放并提供必要的能量来调节巨噬细胞迁移。HIF-1α通过靶向葡萄糖代谢促进巨噬细胞M1极化。此外，HIF-1α诱导糖酵解相关酶以及三羧酸循环和磷酸戊糖途径中间体的上调。HIF-1α促进巨噬细胞凋亡、坏死性凋亡并减少自噬。本综述重点介绍了与巨噬细胞中HIF-1α稳定性调节相关的机制以及HIF-1α在调节巨噬细胞生理功能中的作用。
