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01-02-2018 | Original Article

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

Authors: Claudia Rossi, Valeria Marzano, Ada Consalvo, Mirco Zucchelli, Stefano Levi Mortera, Viviana Casagrande, Maria Mavilio, Paolo Sacchetta, Massimo Federici, Rossella Menghini, Andrea Urbani, Domenico Ciavardelli

Published in: Acta Diabetologica | Issue 2/2018

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.

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Title: Proteomic and metabolomic characterization of streptozotocin-induced diabetic nephropathy in TIMP3-deficient mice
Authors: Claudia Rossi
Valeria Marzano
Ada Consalvo
Mirco Zucchelli
Stefano Levi Mortera
Viviana Casagrande
Maria Mavilio
Paolo Sacchetta
Massimo Federici
Rossella Menghini
Andrea Urbani
Domenico Ciavardelli
Publication date: 01-02-2018
Publisher: Springer Milan
Published in: Acta Diabetologica / Issue 2/2018
Print ISSN: 0940-5429
Electronic ISSN: 1432-5233
DOI: https://doi.org/10.1007/s00592-017-1074-y

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