2. Academic Validation
  3. Regulation of macrophage polarization and glucose metabolism by the ERK/MAPK-HK1 signaling pathway in paraquat-induced acute lung injury

Regulation of macrophage polarization and glucose metabolism by the ERK/MAPK-HK1 signaling pathway in paraquat-induced acute lung injury

  • Chem Biol Interact. 2024 May 18:397:111062. doi: 10.1016/j.cbi.2024.111062.
Mengxuan Li 1,  Qinghuan Ren 2,  Kaiyuan Chen 3,  Ran Yin 1,  Wenwen Li 1,  Zuochun Fang 4,  Sunxiang Liu 4,  Linhua Lan 5,  Guangliang Hong 6
Affiliations

Affiliations

  • 1 Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
  • 2 Wenzhou Medical University, Wenzhou, 325000, China.
  • 3 Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China; Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
  • 4 Longgang Campus of the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
  • 5 Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
  • 6 Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China; Longgang Campus of the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China. Electronic address: honggl98@126.com.
PMID: 38763349 DOI: 10.1016/j.cbi.2024.111062
Abstract

Acute lung injury is the leading cause of paraquat (PQ) poisoning-related mortality. The mechanism by which macrophages are involved in PQ-induced acute lung injury remains unclear. In recent years, the role of metabolic reprogramming in macrophage functional transformation has received significant attention. The current study aimed to identify the role of altered macrophage glucose metabolism and molecular mechanisms in PQ poisoning-induced acute lung injury. We established a model of acute lung injury in PQ-intoxicated mice via the intraperitoneal injection of PQ. PQ exposure induces macrophage M1 polarization and promotes the release of inflammatory factors, which causes the development of acute lung injury in mice. In vitro analysis revealed that PQ altered glucose metabolism, which could be reversed by siRNA transfection to silence the expression of HK1, a key Enzyme in glucose metabolism. RNA Sequencing revealed that the ERK/MAPK pathway was the crucial molecular mechanism of PQ pathogenesis. Further, U0126, an ERK Inhibitor, could inhibit PQ-induced HK1 activation and macrophage M1 polarization. These findings provide novel insights into the previously unrecognized mechanism of ERK/MAPK-HK1 activation in PQ poisoning.

Keywords

Glucose metabolism; Lung injury; Paraquat; Poisoning.

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