MCTR1 alleviates lipopolysaccharide-induced acute lung injury by protecting lung endothelial glycocalyx

Hui Li, Yu Hao, Li Li Yang, Xin Yang Wang, Xin Yu Li, Suwas Bhandari, Jun Han, Yong Jian Liu, Yu Qiang Gong, Aaron Scott, Fang Gao Smith*, Sheng Wei Jin

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)
247 Downloads (Pure)

Abstract

Endothelial glycocalyx degradation, critical for increased pulmonary vascular permeability, is thought to facilitate the development of sepsis into the multiple organ failure. Maresin conjugates in tissue regeneration 1 (MCTR1), a macrophage-derived lipid mediator, which exhibits potentially beneficial effects via the regulation of bacterial phagocytosis, promotion of inflammation resolution, and regeneration of tissue. In this study, we show that MCTR1 (100 ng/mouse) enhances the survival of mice with lipopolysaccharide (LPS)-induced (15 mg/kg) sepsis. MCTR1 alleviates LPS (10 mg/kg)-induced lung dysfunction and lung tissue inflammatory response by decreasing inflammatory cytokines (tumor necrosis factor-α, interleukin-1β [IL-1β], and IL-6) expression in serum and reducing the serum levels of heparan sulfate (HS) and syndecan-1. In human umbilical vein endothelial cells (HUVECs) experiments, MCTR1 (100 nM) was added to the culture medium with LPS for 6 hr. MCTR1 treatment markedly inhibited HS degradation by downregulating heparanase (HPA) protein expression in vivo and in vitro. Further analyses indicated that MCTR1 upregulates sirtuin 1 (SIRT1) expression and decreases NF-κB p65 phosphorylation. In the presence of BOC-2 or EX527, the above effects of MCTR1 were abolished. These results suggest that MCTR1 protects against LPS-induced sepsis in mice by attenuating pulmonary endothelial glycocalyx injury via the ALX/SIRT1/NF-κB/HPA pathway.

Original languageEnglish
Pages (from-to)7283-7294
Number of pages12
JournalJournal of Cellular Physiology
Volume235
Issue number10
Early online date9 Feb 2020
DOIs
Publication statusPublished - Oct 2020

Bibliographical note

© 2020 Wiley Periodicals, Inc.

Keywords

  • endothelial glycocalyx
  • HPA
  • MCTR1
  • sepsis
  • SIRT1
  • Clinical Biochemistry
  • Physiology
  • Cell Biology

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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