Thioredoxin interacting protein expression in the urinary sediment associates with renal function decline in type 1 diabetes

Author(s):Show less -

Monteiro, Maria Beatriz ^[1] ; Santos-Bezerra, Daniele Pereira ^[1] ; Thieme, Karina ^[1] ; Admoni, Sharon Nina ^[1] ; Perez, Ricardo Vessoni ^[1] ; Machado, Cleide Guimaraes ^[2] ; Queiroz, Marcia Silva ^[3] ; Nery, Marcia ^[3] ; Oliveira-Souza, Maria ^[4] ; Woronik, Viktoria ^[5] ; Passarelli, Marisa ^[6] ; Giannella-Neto, Daniel ^[7] ; Machado, Ubiratan Fabres ^[8] ; Correa-Giannella, Maria Lucia ^{[1, 9]}

Affiliation

^[1] Univ Sao Paulo, Fac Med, Lab Endocrinol Celular & Mol LIM 25, BR-01246903 Sao Paulo - Brazil

^[2] FMUSP, Hosp Clin, Div Oftalmol, Sao Paulo - Brazil

^[3] FMUSP, Hosp Clin, Div Endocrinol, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Inst Ciencias Biomed, Dept Fisiol & Biofis, Lab Fisiol Renal, BR-01246903 Sao Paulo - Brazil

^[5] FMUSP, Hosp Clin, Div Nefrol, Sao Paulo - Brazil

^[6] FMUSP, Lab Lipides LIM 10, Sao Paulo - Brazil

^[7] Univ Nove Julho Uninove, Programa Posgrad Med, Sao Paulo - Brazil

^[8] ICBUSP, Dept Fisiol & Biofis, Lab Metab & Endocrinol, Sao Paulo - Brazil

^[9] FMUSP, Nucleo Terapia Celular & Mol NUCEL NETCEM, Sao Paulo - Brazil

• Document type: Journal article
• Source: Free Radical Research; v. 50, n. 1, p. 101-110, JAN 2 2016.
• Web of Science Citations: 9

Abstract

Aims: Thioredoxin interacting protein (TXNIP), an inhibitor of antioxidant thioredoxin (Trx), is upregulated by hyperglycemia and implicated in pathogenesis of diabetes complications. We evaluated mRNA expressions of genes encoding TXNIP and Trx (TXN) in urinary sediment and peripheral blood mononuclear cells (PBMC) of type 1 diabetes (T1D) patients with different degrees of chronic complications. Methods: qPCR was employed to quantify target genes in urinary sediment (n=55) and PBMC (n=161) from patients sorted by presence or absence of diabetic nephropathy (DN), retinopathy, peripheral and cardiovascular neuropathy; 26 healthy controls and 13 patients presenting non-diabetic nephropathy (focal and segmental glomerulosclerosis, FSGS) were also included. Results: Regarding the urinary sediment, TXNIP (but not TXN) expression was higher in T1D (p=0.0023) and FSGS (p=0.0027) patients versus controls. Expressions of TXNIP and TXN were higher, respectively, in T1D patients with versus without DN (p=0.032) and in those with estimated glomerular filtration rate (eGFR) <60 versus >= 60 mL/min/1.73 m(2) (p=0.008). eGFR negatively correlated with TXNIP (p=0.04, r=-0.28) and TXN (p=0.04, r=-0.30) expressions. T1D patients who lost >= 5 mL/min/1.73 m(2) yearly of eGFR presented higher basal TXNIP expression than those who lost<5 mL/min/1.73 m(2) yearly after median follow-up of 24 months. TXNIP (p<0.0001) and TXN (p=0.002) expressions in PBMC of T1D patients were significantly higher than in controls but no differences were observed between patients with or without chronic complications. Conclusions: TXNIP and TXN are upregulated in urinary sediment of T1D patients with diabetic kidney disease (DKD), but only TXNIP expression is associated with magnitude of eGFR decline. (AU)

• FAPESP's process: 13/19569-3 - Effects of endothelin-3 and leptin in renal morphology and function in vivo: involvement of the intrarenal renin-angiotensin system
• Grantee: Maria Oliveira de Souza
• Support type: Regular Research Grants
• FAPESP's process: 12/02003-4 - 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
• Grantee: Maria Beatriz Camargo Monteiro Caillaud
• Support type: Scholarships in Brazil - Doctorate
• FAPESP's process: 12/04831-1 - New players in glycemic control and chronic complications of Diabetes mellitus: preventive and therapeutic perspectives
• Grantee: Ubiratan Fabres Machado
• Support type: Research Projects - Thematic Grants
• FAPESP's process: 12/05583-1 - 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
• Grantee: Maria Lucia Cardillo Corrêa Giannella
• Support type: Regular Research Grants
• FAPESP's process: 12/25490-8 - Lower expression of advanced glycation endproduts receptor-1 (AGER1) in peripheral blood mononuclear cells is associated with renal disease in type 1 diabetes patients
• Grantee: Daniele Pereira dos Santos Bezerra
• Support type: Scholarships in Brazil - Master