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Publication : Protective role for kidney TREM2(high) macrophages in obesity- and diabetes-induced kidney injury.

First Author  Subramanian A Year  2024
Journal  Cell Rep Volume  43
Issue  6 Pages  114253
PubMed ID  38781074 Mgi Jnum  J:351693
Mgi Id  MGI:7665964 Doi  10.1016/j.celrep.2024.114253
Citation  Subramanian A, et al. (2024) Protective role for kidney TREM2(high) macrophages in obesity- and diabetes-induced kidney injury. Cell Rep 43(6):114253
abstractText  Diabetic kidney disease (DKD), the most common cause of kidney failure, is a frequent complication of diabetes and obesity, and yet to date, treatments to halt its progression are lacking. We analyze kidney single-cell transcriptomic profiles from DKD patients and two DKD mouse models at multiple time points along disease progression-high-fat diet (HFD)-fed mice aged to 90-100 weeks and BTBR ob/ob mice (a genetic model)-and report an expanding population of macrophages with high expression of triggering receptor expressed on myeloid cells 2 (TREM2) in HFD-fed mice. TREM2(high) macrophages are enriched in obese and diabetic patients, in contrast to hypertensive patients or healthy controls in an independent validation cohort. Trem2 knockout mice on an HFD have worsening kidney filter damage and increased tubular epithelial cell injury, all signs of worsening DKD. Together, our studies suggest that strategies to enhance kidney TREM2(high) macrophages may provide therapeutic benefits for DKD.
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