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Expression of mRNA of the TXNIP, SCL19A2 and SCL19A3 genes in the urinary sediment of patients with type 1 diabetes with and without diabetic nephropathy

Grant number: 12/02003-4
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): July 01, 2012
Effective date (End): December 31, 2015
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Maria Lucia Cardillo Corrêa Giannella
Grantee:Maria Beatriz Camargo Monteiro Caillaud
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Diabetic nephropathy (DN) is classically divided into five stages, with the following characteristics: 1) glomerular hyperfiltration, 2) normal urinary albumin excretion (UAE), 3) incipient DN with persistent microalbuminuria, 4) overt DN characterized by proteinuria and decreased glomerular filtration rate (GFR) and 5) end stage renal disease (ESRD). Several studies have shown, however, that UAE and the decline in renal function may not evolve in parallel and that GFR may decrease in the absence of abnormal UAE. In addition, recent evidence suggests that in patients with chronic kidney disease (CKD), the extent of renal dysfunction seems to correlate better with tubulointerstitial injury than with glomerulopathy. It is known that concentrations of oxidative stress markers are increased in diabetic patients. The thioredoxin (Trx) system is a major endogenous antioxidant system. TRX is able to interact with a large number of transcription factors and proteins such as Trx interacting protein (TXNIP). Recently, the involvement of TXNIP has been recognized in the pathogenesis of diabetes mellitus (DM) and its complications. Data indicate that this protein plays an important role in the progression of DN. Deficiency of thiamine, or B1 vitamin, has been reported in experimental models of diabetes concomitantly with an increase in its renal clearance. Thiamine transporter 1 (THTR-1), encoded by the SLC19A2 gene and Thiamine transporter 2 (THTR-2), encoded by the SLC19A3 gene are responsible for thiamine reabsorption in the proximal tubule after glomerular filtration. Studies have shown that increased urinary excretion of thiamine may be a risk predictor for an early decline in kidney function in diabetic patients. The objective of this study is to evaluate the role of the genes TXNIP, SLC19A2 and SLC19A3 in the pathogenesis of DN in patients with type 1 DM. To this end, messenger RNA (mRNA) will be extracted from the urinary sediment of diabetic patients to assess the expression of target genes, that will be associated with the clinical manifestations of ND, in four groups of patients: (1) normoalbuminuria and GFR> 60 mL /min (2) microalbuminuria and GFR <60 mL /min, (3) macroalbuminuria and GFR> 60 mL /min and (4) macroalbuminuria and GFR <60 mL/min. The study of activation or inactivation of intrarenal pathways potentially associated with progression of DN in humans is complicated by the need for renal biopsy. With the recent development of reliable techniques for extracting RNA from the urinary sediment and RT-qPCR, mRNA analysis of urinary sediment can become a tool in the evaluation of renal diseases, both in an attempt to identify biomarkers that can predict the evolution of renal function as well as for a better understanding of the pathogenesis of this complication.

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MONTEIRO, MARIA BEATRIZ; THIEME, KARINA; SANTOS-BEZERRA, DANIELE PEREIRA; QUEIROZ, MARCIA SILVA; WORONIK, VIKTORIA; PASSARELLI, MARISA; MACHADO, UBIRATAN FABRES; GIANNELLA-NETO, DANIEL; OLIVEIRA-SOUZA, MARIA; CORREA-GIANNELLA, MARIA LUCIA. Beta-2-microglobulin (B2M) expression in the urinary sediment correlates with clinical markers of kidney disease in patients with type 1 diabetes. METABOLISM-CLINICAL AND EXPERIMENTAL, v. 65, n. 6, p. 816-824, JUN 2016. Web of Science Citations: 8.
MONTEIRO, MARIA BEATRIZ; SANTOS-BEZERRA, DANIELE PEREIRA; THIEME, KARINA; ADMONI, SHARON NINA; PEREZ, RICARDO VESSONI; MACHADO, CLEIDE GUIMARAES; QUEIROZ, MARCIA SILVA; NERY, MARCIA; OLIVEIRA-SOUZA, MARIA; WORONIK, VIKTORIA; PASSARELLI, MARISA; GIANNELLA-NETO, DANIEL; MACHADO, UBIRATAN FABRES; CORREA-GIANNELLA, MARIA LUCIA. Thioredoxin interacting protein expression in the urinary sediment associates with renal function decline in type 1 diabetes. Free Radical Research, v. 50, n. 1, p. 101-110, JAN 2 2016. Web of Science Citations: 9.
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
CAILLAUD, Maria Beatriz Camargo Monteiro. The expression of the genes encoding thioredoxin interacting protein, beta 2 microglobulin and thiamine transporter 1, correlates with clinical markers of renal disease in type 1 diabetes patients. 2016. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina São Paulo.

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