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MCTR1 alleviates lipopolysaccharide‐induced acute lung injury by protecting lung endothelial glycocalyx
Author(s) -
Li Hui,
Hao Yu,
Yang LiLi,
Wang XinYang,
Li XinYu,
Bhandari Suwas,
Han Jun,
Liu YongJian,
Gong YuQiang,
Scott Aaron,
Smith Fang Gao,
Jin ShengWei
Publication year - 2020
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.29628
Subject(s) - lipopolysaccharide , glycocalyx , umbilical vein , tumor necrosis factor alpha , sepsis , inflammation , chemistry , in vivo , human umbilical vein endothelial cell , sirtuin 1 , pharmacology , immunology , microbiology and biotechnology , medicine , biology , in vitro , downregulation and upregulation , biochemistry , gene
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.