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

Hao Liu; Lu Zhang; Zhen Liu; Jinyuan Lin; Xiaojing He; Siyi Wu; Yi Qin; Chen Zhao; Youyuan Guo; Fei Lin

doi:10.1016/j.isci.2023.107496

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

iScience. 2023 Jul 28;26(9):107496. doi: 10.1016/j.isci.2023.107496. eCollection 2023 Sep 15.

Authors

Hao Liu^{1

2

3

4}, Lu Zhang^{1

2

3

4}, Zhen Liu^{1

2

3

4}, Jinyuan Lin^{1

2

3

4}, Xiaojing He^{1

2

3

4}, Siyi Wu^{1

2

3

4}, Yi Qin^{1

2

3

4}, Chen Zhao^{1

2

3

4}, Youyuan Guo^{1

2

3

4}, Fei Lin^{1

2

3

4}

Affiliations

¹ Department of Anesthesiology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, China.
² Guangxi Clinical Research Center for Anesthesiology(GK AD22035214), Nanning, Guangxi 530021, China.
³ Guangxi Engineering Research Center for Tissue & Organ Injury and Repair Medicine, Nanning, Guangxi 530021, China.
⁴ Guangxi Health Commission Key Laboratory of Basic Science and Prevention of Perioperative Organ Disfunction, Nanning, Guangxi 530021, China.

Abstract

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.

Keywords: Clinical genetics; Molecular medicine; Pathology.