An adoptive cell therapy with TREM2‐overexpressing macrophages mitigates the transition from acute kidney injury to chronic kidney disease DOI Creative Commons
Yating Zhang, Jie Liu, Siweier Luo

et al.

Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(3)

Published: Feb. 25, 2025

Abstract Background Macrophages have been shown to contribute renal injury and fibrosis as well repair. Recently, Triggering Receptor Expressed on Myeloid Cells 2 (TREM2)‐positive macrophages play important roles in regulating tissue inflammation However, it remains unclear whether they can mitigate the transition from acute kidney chronic disease (the AKI–CKD transition). Methods The was generated by unilateral ischaemia–reperfusion (UIRI) wild‐type (WT) Trem2 knockout mice. F4/80 magnetic beads were used isolate macrophages. Flow cytometry determine levels of TREM2 CD11b levels. Quantitative reverse transcription polymerase chain reaction (qRT‐PCR), Western blotting histological staining performed expression cytokines fibrotic markers. RNA‐seq investigate transcriptomic changes between WT bone marrow‐derived (BMDMs). TREM2‐overexpressing using lentivirus transferred intravenously UIRI Results exhibited a strong protective effect transition. Genetic deletion resulted increased exacerbated Interestingly, we found that hypoxia could increase via HIF‐1α. Upregulated enhanced macrophage phagocytosis suppressed pro‐inflammatory cytokines, resulting lower apoptosis tubular epithelial cells. Using analysis, showed regulatory effects orchestrated PI3K‐AKT pathway. Pharmacological regulation pathway modulate macrophage‐mediated phagocytosis. In addition, an adoptive cell therapy effectively reduced immune infiltration, Conclusion Our study not only provides valuable mechanistic insights into role but also offers new avenue for macrophage‐based treat diseases. Key points worsens accelerates is upregulated HIF1α An reduces fibrosis.

Language: Английский

An adoptive cell therapy with TREM2‐overexpressing macrophages mitigates the transition from acute kidney injury to chronic kidney disease DOI Creative Commons
Yating Zhang, Jie Liu, Siweier Luo

et al.

Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(3)

Published: Feb. 25, 2025

Abstract Background Macrophages have been shown to contribute renal injury and fibrosis as well repair. Recently, Triggering Receptor Expressed on Myeloid Cells 2 (TREM2)‐positive macrophages play important roles in regulating tissue inflammation However, it remains unclear whether they can mitigate the transition from acute kidney chronic disease (the AKI–CKD transition). Methods The was generated by unilateral ischaemia–reperfusion (UIRI) wild‐type (WT) Trem2 knockout mice. F4/80 magnetic beads were used isolate macrophages. Flow cytometry determine levels of TREM2 CD11b levels. Quantitative reverse transcription polymerase chain reaction (qRT‐PCR), Western blotting histological staining performed expression cytokines fibrotic markers. RNA‐seq investigate transcriptomic changes between WT bone marrow‐derived (BMDMs). TREM2‐overexpressing using lentivirus transferred intravenously UIRI Results exhibited a strong protective effect transition. Genetic deletion resulted increased exacerbated Interestingly, we found that hypoxia could increase via HIF‐1α. Upregulated enhanced macrophage phagocytosis suppressed pro‐inflammatory cytokines, resulting lower apoptosis tubular epithelial cells. Using analysis, showed regulatory effects orchestrated PI3K‐AKT pathway. Pharmacological regulation pathway modulate macrophage‐mediated phagocytosis. In addition, an adoptive cell therapy effectively reduced immune infiltration, Conclusion Our study not only provides valuable mechanistic insights into role but also offers new avenue for macrophage‐based treat diseases. Key points worsens accelerates is upregulated HIF1α An reduces fibrosis.

Language: Английский

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