HIF1<i>α</i>-Induced Glycolysis Metabolism Is Essential to the Activation of Inflammatory Macrophages

  • Ting Wang
    Department of Physiology and Pathophysiology, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, School of Basic Medical Sciences, Peking University, Beijing 100191, China
  • Huiying Liu
    Department of Physiology and Pathophysiology, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, School of Basic Medical Sciences, Peking University, Beijing 100191, China
  • Guan Lian
    Department of Physiology and Pathophysiology, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, School of Basic Medical Sciences, Peking University, Beijing 100191, China
  • Song-Yang Zhang
    Department of Physiology and Pathophysiology, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, School of Basic Medical Sciences, Peking University, Beijing 100191, China
  • Xian Wang
    Department of Physiology and Pathophysiology, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, School of Basic Medical Sciences, Peking University, Beijing 100191, China
  • Changtao Jiang
    Department of Physiology and Pathophysiology, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, School of Basic Medical Sciences, Peking University, Beijing 100191, China

抄録

<jats:p>Hypoxia-inducible factor (HIF) 1<jats:italic>α</jats:italic>is a metabolic regulator that plays an important role in immunologic responses. Previous studies have demonstrated that HIF1<jats:italic>α</jats:italic>participates in the M1 polarization of macrophages. To clarify the mechanism of HIF1<jats:italic>α</jats:italic>-induced polarization of M1 macrophage, myeloid-specific HIF1<jats:italic>α</jats:italic>overexpression (Lysm HIF1<jats:italic>α</jats:italic>lsl) mice were employed and the bone marrow-derived and peritoneal macrophages were isolated. RT-PCR results revealed that HIF1<jats:italic>α</jats:italic>overexpression macrophage had a hyperinflammatory state characterized by the upregulation of M1 markers. Cellular bioenergetics analysis showed lower cellular oxygen consumption rates in the Lysm HIF1<jats:italic>α</jats:italic>lsl mice. Metabolomics studies showed that HIF1<jats:italic>α</jats:italic>overexpression led to increased glycolysis and pentose phosphate pathway intermediates. Further results revealed that macrophage M1 polarization, induced by HIF1<jats:italic>α</jats:italic>overexpression, was via upregulating the mRNA expression of the genes related to the glycolysis metabolism. Our results indicate that HIF1<jats:italic>α</jats:italic>promoted macrophage glycolysis metabolism, which induced M1 polarization in mice.</jats:p>

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