Proteomic and metabolomic characterization of streptozotocin-induced diabetic nephropathy in TIMP3-deficient mice

C. Rossi, V. Marzano, A. Consalvo, M. Zucchelli, S. Levi Mortera, V. Casagrande, M. Mavilio, P. Sacchetta, M. Federici, R. Menghini, A. Urbani, D. Ciavardelli

Research output: Contribution to journalArticlepeer-review

Abstract

Aims: The tissue inhibitor of metalloproteinase TIMP3 is a stromal protein that restrains the activity of both protease and receptor in the extracellular matrix and has been found to be down-regulated in diabetic nephropathy (DN), the leading cause of end-stage renal disease in developed countries. Methods: In order to gain deeper insights on the association of loss of TIMP3 and DN, we performed differential proteomic analysis of kidney and blood metabolic profiling of wild-type and Timp3-knockout mice before and after streptozotocin (STZ) treatment, widely used to induce insulin deficiency and hyperglycemia. Results: Kidney proteomic data and blood metabolic profiles suggest significant alterations of peroxisomal and mitochondrial fatty acids β-oxidation in Timp3-knockout mice compared to wild-type mice under basal condition. These alterations were exacerbated in response to STZ treatment. Conclusions: Proteomic and metabolomic approaches showed that loss of TIMP3 alone or in combination with STZ treatment results in significant alterations of kidney lipid metabolism and peripheral acylcarnitine levels, supporting the idea that loss of TIMP3 may generate a phenotype more prone to DN. © 2017, Springer-Verlag Italia S.r.l., part of Springer Nature.
Original languageEnglish
Pages (from-to)121-129
Number of pages9
JournalActa Diabetologica
Volume55
Issue number2
DOIs
Publication statusPublished - 2018

Keywords

  • acylcarnitine
  • fatty acid
  • streptozocin
  • tissue inhibitor of metalloproteinase 3
  • proteome
  • tissue inhibitor of metalloproteinase 3, animal experiment
  • animal model
  • animal tissue
  • Article
  • blood
  • controlled study
  • diabetic nephropathy
  • fatty acid oxidation
  • infant
  • kidney
  • lipid metabolism
  • metabolomics
  • mitochondrion
  • mouse
  • nonhuman
  • peroxisome
  • priority journal
  • proteomics
  • streptozotocin-induced diabetes mellitus
  • animal
  • C57BL mouse
  • chemically induced
  • chronic kidney failure
  • complication
  • experimental diabetes mellitus
  • genetics
  • knockout mouse
  • metabolism
  • metabolome
  • pathology, Animals
  • Diabetes Mellitus, Experimental
  • Diabetic Nephropathies
  • Kidney
  • Kidney Failure, Chronic
  • Lipid Metabolism
  • Metabolome
  • Metabolomics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Proteome
  • Proteomics
  • Streptozocin
  • Tissue Inhibitor of Metalloproteinase-3

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