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Non-invasive Imaging of Acute Allograft Rejection after Rat Renal Transplantation Using 18F-FDG PET
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Non-invasive Imaging of Acute Allograft Rejection after Rat Renal Transplantation Using 18F-FDG PET

Published on: April 28, 2013

Modulation of matrix gelatinases and metalloproteinase-activating process in acute kidney rejection

Alain Laplante1, Dingyi Liu, Michel Demeule

  • 1Laboratory of Molecular Medicine, UQAM-Sainte-Justine Hospital, C.P. 8888, Succursale Centre-Ville Montreal, Quebec, H3C 3P8, Canada.

Transplant International : Official Journal of the European Society for Organ Transplantation
|May 6, 2003
PubMed

Insights

Matrix metalloproteinase (MMP) activity changes contribute to kidney allograft rejection. Altered MMP-2 processing, linked to decreased TIMP-2, occurs during acute rejection, impacting extracellular matrix accumulation.

Area of Science:

  • Nephrology
  • Immunology
  • Biochemistry

Background:

  • Matrix metalloproteinases (MMPs) play a role in extracellular matrix remodeling.
  • Altered MMP activity is implicated in kidney allograft rejection and fibrosis.
  • Understanding MMP involvement is crucial for managing rejection.

Purpose of the Study:

  • To investigate the role of MMP-2, MMP-9, and their inhibitors in acute kidney allograft rejection.
  • To analyze changes in gelatinolytic activity in rejected grafts and urine.
  • To elucidate the processing of proMMP-2 in the context of TIMP-2 and MT1-MMP during rejection.

Main Methods:

  • Zymography and fluorescence assays to assess gelatinolytic activity in rat kidney allografts and urine.
  • Immunodetection to quantify MMP-2, MT1-MMP, and TIMP-2 protein levels.
  • Orthotopic kidney allotransplantation model (Buffalo to Wistar-Furth rats).

Main Results:

  • Increased proMMP-2 activity and protein levels in rejected grafts compared to controls.
  • Decreased activated MMP-2 and significantly reduced TIMP-2 protein levels during rejection.
  • Undetectable MT1-MMP proteolytic fragments and altered proMMP-2 processing.
  • Reduced overall urinary gelatinolytic activity, with a novel 78-kDa protein activity emerging post-transplantation.

Conclusions:

  • Diminished TIMP-2 levels in acute kidney rejection impair MT1-MMP-dependent processing of proMMP-2 to active MMP-2.
  • These MMP alterations contribute to extracellular matrix accumulation in rejecting allografts.
  • Urinary MMP profiles may serve as potential biomarkers for kidney transplant rejection.

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