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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Tissue-resident natural killer cells exacerbate tubulointerstitial fibrosis by activating transglutaminase 2 and syndecan-4 in a model of aristolochic acid-induced nephropathy

  • Wee, Yu Mee (Department of Asan Institute for Life Science, Asan Medical Center) ;
  • Go, Heounjeong (Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Choi, Monica Young (Department of Asan Institute for Life Science, Asan Medical Center) ;
  • Jung, Hey Rim (Department of Asan Institute for Life Science, Asan Medical Center) ;
  • Cho, Yong Mee (Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Kim, Young Hoon (Division of Kidney and Pancreas Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Han, Duck Jong (Division of Kidney and Pancreas Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Shin, Sung (Department of Asan Institute for Life Science, Asan Medical Center)
  • Received : 2018.08.23
  • Accepted : 2018.12.26
  • Published : 2019.09.30
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Abstract

Despite reports suggesting that tissue-resident natural killer (trNK) cells cause ischemic kidney injury, their contribution to the development of tubulointerstitial fibrosis has not been determined. This study hypothesized that the depletion of trNK cells may ameliorate renal fibrosis by affecting transglutaminase 2/syndecan-4 interactions. Aristolochic acid nephropathy (AAN) was induced in C57BL/6 mice as an experimental model of kidney fibrosis. The mice were treated with anti-asialo GM1 (ASGM1) or anti-NK1.1 antibodies to deplete NK cells. Although both ASGM1 and NK1.1 antibodies suppressed renal $NKp46^+DX5^+$ NK cells, renal $NKp46^+DX5^-$ cells were resistant to suppression by ASGM1 or NK1.1 antibodies during the development of tubulointerstitial fibrosis in the AAN-induced mouse model. Western blot analysis showed that both antibodies increased the expression of fibronectin, transglutaminase 2, and syndecan-4. These findings indicate that trNK cells played an exacerbating role in tubulointerstitial fibrosis by activating transglutaminase 2 and syndecan-4 in the AAN-induced mouse model.

Keywords

References

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