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

Autor(es):Mostrar menos -

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]}

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: Free Radical Research; v. 50, n. 1, p. 101-110, JAN 2 2016.
• Citações Web of Science: 9

Resumo

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)

• Processo FAPESP: 12/25490-8 - A menor expressão do RNA mensageiro do receptor 1 de produtos finais de glicação avançada (AGER1) em células linfomononucleares de sangue periférico está associada à doença renal em portadores de diabetes mellitus tipo 1
• Beneficiário: Daniele Pereira dos Santos Bezerra
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 13/19569-3 - Efeitos da endotelina 3 e da leptina na morfologia e função renal in vivo: participação do sistema renina-angiotensina intrarrenal
• Beneficiário: Maria Oliveira de Souza
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/05583-1 - Expressão do RNA mensageiro dos genes TXNIP, SCL19A2 e SCL19A3 no sedimento urinário de portadores de Diabetes mellitus tipo 1 com e sem nefropatia diabética
• Beneficiário: Maria Lucia Cardillo Corrêa Giannella
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/04831-1 - Novos moduladores do controle glicêmico e do desenvolvimento de complicações crônicas no Diabetes mellitus: perspectivas preventivas e terapêuticas
• Beneficiário: Ubiratan Fabres Machado
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 12/02003-4 - Expressão do RNA mensageiro dos genes TXNIP, SCL19A2 e SCL19A3 no sedimento urinário de portadores de diabetes mellitus tipo 1 com e sem nefropatia diabética
• Beneficiário: Maria Beatriz Camargo Monteiro Caillaud
• Modalidade de apoio: Bolsas no Brasil - Doutorado