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- W2615071954 abstract "Introduction: The interaction of transglutaminase 2 and the heparan sulfate proteoglycan syndecan-4 causes the development of renal fibrosis in chronic kidney diseases. Despite a few reports postulating a causal effect of tissue-resident natural killer (trNK) cells on ischemic kidney injury, their contribution to the development of tubulointerstitial fibrosis has yet to be tested. It is our hypothesis that trNK depletion by anti-NK1.1 antibody treatment might ameliorate renal fibrosis by affecting the transglutaminase 2/syndecan-4 interaction. Methods: C57BL/6 mice treated with anti-asialo GM1 or NK 1.1 antibody were evaluated for tubulointerstitial fibrosis in the aristolochic acid nephropathy (AAN) model (Figure 1). Results: Although sustained NK 1.1 antibody treatment maintained both renal CD56 + DX5+ and CD56 + DX5− natural killer cell suppression, renal CD56 + DX5− natural killer cells remained during the development of tubulointerstitial fibrosis by anti-asialo GM1 antibody treatment in the AAN model (Figure 2). Tubulointerstitial fibrosis was exacerbated in the group with AAN and anti-asialo GM1 antibody treatment compared with the AAN group. Interestingly, tubulointerstitial fibrosis was attenuated in the group with AAN and NK1.1 antibody treatment compared with the AAN and anti-asialo GM1 antibody treatment group (Figure 3). Western blot analysis revealed that NK1.1 antibody treatment decreased the activities of syndecan-4 but had no effect on the intensity of transglutaminase 2 and interferon-gamma. Conclusions: Tissue–resident natural killer cells exacerbate tubulointerstitial fibrosis by activation of syndecan-4 in the AAN model and are depleted by anti-NK1.1 antibody. This work has been supported by a Korean SGER (Small Grant Exploratory Research) project (2014R1A1A2A16055405) to S.S. from the National Research Foundation of Korea.FigureFigureFigure" @default.
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- W2615071954 date "2017-05-01" @default.
- W2615071954 modified "2023-10-17" @default.
- W2615071954 title "Tissue–Resident Natural Killer Cells Exacerbate Tubulointerstitial Fibrosis by activation of Syndecan-4 in Aristolochic Acid Nephropathy Models and are Depleted by Anti-NK1.1 Antibody" @default.
- W2615071954 doi "https://doi.org/10.1097/01.tp.0000520389.08603.00" @default.
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