Peroxiredoxin 3 has a crucial role in the macrophage polarization by regulating mitochondrial homeostasis.

Wenhui Huang, Lianfang Wang, Zhipeng Huang, Zhichao Sun, Bojun Zheng
Author Information
  1. Wenhui Huang: Department of Respiratory and Critical Care Medicine, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
  2. Lianfang Wang: Department of Respiratory and Critical Care Medicine, Guangxi Hospital Division of The First Affiliated Hospital, Sun Yat-sen University, Guangxi, China.
  3. Zhipeng Huang: Dongguan Hospital of Integrated Chinese and Western Medicine, Dongguan, China.
  4. Zhichao Sun: The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
  5. Bojun Zheng: Department of Critical Care Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. zhengbojun@gzucm.edu.cn.

Abstract

Acute lung injury (ALI) is one of the life-threatening complications of sepsis, and macrophage polarization plays a crucial role in the sepsis-associated ALI. However, the regulatory mechanisms of macrophage polarization in ALI and in the development of inflammation are largely unknown. In this study, we demonstrated that macrophage polarization occurs in sepsis-associated ALI and is accompanied by mitochondrial dysfunction and inflammation, and a decrease of PRDX3 promotes the initiation of macrophage polarization and mitochondrial dysfunction. Mechanistically, PRDX3 overexpression promotes M1 macrophages to differentiate into M2 macrophages, and enhances mitochondrial functional recovery after injury by reducing the level of glycolysis and increasing TCA cycle activity. In conclusion, we identified PRDX3 as a critical hub integrating oxidative stress, inflammation, and metabolic reprogramming in macrophage polarization. The findings illustrate an adaptive mechanism underlying the link between macrophage polarization and sepsis-associated ALI.

Keywords

References

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Grants

  1. 202201020315/Science and Technology Program of Guangzhou
  2. 20222065/The Guangdong Provincial Bureau of Traditional Chinese Medicine
  3. 82104989/National Outstanding Youth Science Fund Project of National Natural Science Foundation of China

MeSH Term

Humans
Acute Lung Injury
Inflammation
Lipopolysaccharides
Macrophages
Mitochondrial Diseases
Peroxiredoxin III
Sepsis
Animals
Mice

Chemicals

Lipopolysaccharides
Peroxiredoxin III
Prdx3 protein, mouse

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