Galectin-3 as TREM2 upstream factor contributes to lung ischemia-reperfusion injury by regulating macrophage polarization

• Published in: iScience 2023-09, Vol.26 (9), p.107496-107496, Article 107496
• Main Authors: Liu, Hao, Zhang, Lu, Liu, Zhen, Lin, Jinyuan, He, Xiaojing, Wu, Siyi, Qin, Yi, Zhao, Chen, Guo, Youyuan, Lin, Fei
• Format: Article
• Language: English
• Subjects: Clinical genetics; Molecular medicine; Pathology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2023.107496

Lung ischemia-reperfusion injury (LIRI) is a complex “aseptic” inflammatory response, macrophage play a pivotal role in the pathogenesis of LIRI. Galectin-3 (Gal3), a lectin implicated inflammation, has received limited attention in LIRI. Studies have reported Gal3 as a ligand for triggering receptor expressed on myeloid cell 2 (TREM2) in macrophages in Alzheimer’s disease. Hence, we established LIRI C57BL/6 mice model and hypoxia/glucose deprivation and reoxygenation (OGD/R) model to investigate the relationship among Gal3, TREM2, and macrophage polarization. Our result demonstrated inhibition of Gal3 significantly reduced M1-type macrophage polarization while markedly increased M2-type in LIRI. In addition, we observed colocalization of Gal3 and TREM2 in macrophages, inhibition of Gal3 could recover the downregulation of TREM2 induced by LIRI while promoting TREM2 expression could attenuate lung injury in LIRI. In summary, our findings suggest Gal3 as an upstream factor of TREM2, play a crucial role in LIRI by regulating macrophage polarization. [Display omitted] •Gal3 and TREM2 co-locate in macrophages•Inhibition of Gal3 recovers the downregulation of TREM2 in LIRI models•Inhibition of Gal3 and excitation of TREM2 can reduce LIRI lung injury Clinical genetics; Pathology; Molecular medicine