Claudia Rossi1,2, Valeria Marzano3,4, Ada Consalvo5,6, Mirco Zucchelli5, Stefano Levi Mortera3,4, Viviana Casagrande7, Maria Mavilio7, Paolo Sacchetta5,6, Massimo Federici7, Rossella Menghini7, Andrea Urbani3,8, Domenico Ciavardelli5,9. 1. Laboratorio di Biochimica Analitica e Proteomica, Centro Scienze dell'Invecchiamento e Medicina Traslazionale - CeSI-MeT, Via Luigi Polacchi 11, 66100, Chieti, Italy. claudia.rossi@unich.it. 2. Department of Medical, Oral and Biotechnological Sciences, "G. d'Annunzio" University of Chieti-Pescara, Via dei Vestini 29, 66013, Chieti, Italy. claudia.rossi@unich.it. 3. Proteomic and Metabonomic Laboratory, Santa Lucia Foundation IRCCS, Via del Fosso di Fiorano 65, 00143, Rome, Italy. 4. Human Microbiome Unit, Genetic and Rare Diseases Area, Bambino Gesù Children's Hospital IRCCS, Piazza S. Onofrio 4, 00165, Rome, Italy. 5. Laboratorio di Biochimica Analitica e Proteomica, Centro Scienze dell'Invecchiamento e Medicina Traslazionale - CeSI-MeT, Via Luigi Polacchi 11, 66100, Chieti, Italy. 6. Department of Medical, Oral and Biotechnological Sciences, "G. d'Annunzio" University of Chieti-Pescara, Via dei Vestini 29, 66013, Chieti, Italy. 7. Department of Systems Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133, Rome, Italy. 8. Institute of Biochemistry and Biochemical Clinic, Faculty of Medicine and Surgery - Policlinico A. Gemelli, Catholic University of Sacred Heart, Largo F. Vito 1, 00168, Rome, Italy. 9. School of Human and Social Science, 'Kore' University of Enna, Via della Cooperazione, 94100, Enna, Italy.
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.
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.
Authors: Mingmei Shao; Hao Lu; Ming Yang; Yang Liu; Peihao Yin; Guowen Li; Yunman Wang; Lin Chen; Qingguang Chen; Cheng Zhao; Qun Lu; Tao Wu; Guang Ji Journal: Ann Transl Med Date: 2020-03