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Updated: Mar 9, 2026

Phenotypic Characterization of Macrophages from Rat Kidney by Flow Cytometry
Published on: October 18, 2016
TREM2 in Macrophages Promotes Renal Fibrosis via Activation of β-Catenin Signalling Pathway in Obstructive
Jia Wei1, Zixia Li1, Gengyu Du1
1Department of Urology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.
Abstract:
Obstructive nephropathy leads to renal fibrosis, and Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) drives this macrophage-mediated process, but its mechanism remains unclear. This study investigated TREM2's role in macrophage polarisation and renal fibrosis progression. In human fibrotic kidneys, TREM2 expression was significantly elevated and co-localised with macrophages. Unilateral ureteral obstruction (UUO) modelling in mice recapitulated this upregulation, accompanied by renal fibrosis, M2 macrophage polarisation and glomerular filtration rate (GFR) reduction. Trem2 deficiency (Trem2 -/- ) significantly attenuated these pathological changes in UUO mice, preserving GFR. Separately, TREM2 inhibitory peptide sequence IA9 administration reduced renal fibrosis and M2 polarisation in UUO mice. In bone marrow-derived macrophages (BMDMs), Trem2 deficiency suppressed IL-4/IL-13-induced M2 polarisation, migration and β-catenin expression. Critically, lithium chloride (LiCl)-mediated β-catenin stabilisation rescued these impairments in Trem2 -/- BMDMs. In conclusion, TREM2 promotes renal fibrosis by activating β-catenin signalling to drive profibrotic M2 macrophage responses, establishing TREM2 blockade as a therapeutic strategy for obstructive nephropathy.
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