Hypoxia inducible factor-1α is an important regulator of macrophage biology
Bingquan Qiu,
Piaoliu Yuan,
Xiaojuan Du,
Hongfang Jin,
Junbao Du,
Yaqian Huang
Affiliations
Bingquan Qiu
Department of Pediatrics, Peking University First Hospital, Beijing, 100034, China; State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, 100191, China
Piaoliu Yuan
Department of Pediatrics, Peking University First Hospital, Beijing, 100034, China; State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, 100191, China
Xiaojuan Du
Department of Pediatrics, Peking University First Hospital, Beijing, 100034, China; State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, 100191, China
Hongfang Jin
Department of Pediatrics, Peking University First Hospital, Beijing, 100034, China; State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, 100191, China
Junbao Du
Department of Pediatrics, Peking University First Hospital, Beijing, 100034, China; State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, 100191, China
Yaqian Huang
Department of Pediatrics, Peking University First Hospital, Beijing, 100034, China; State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, 100191, China; Corresponding author. Department of Pediatrics, Peking University First Hospital, Beijing, 100034, China.
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 in vivo and in vitro. 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.
