Maria Beatriz Monteiro1, Daniele Pereira Santos-Bezerra1, Karina Thieme1, Sharon Nina Admoni1, Ricardo Vessoni Perez1, Cleide Guimarães Machado2, Marcia Silva Queiroz3, Marcia Nery3, Maria Oliveira-Souza4, Viktoria Woronik5, Marisa Passarelli6, Daniel Giannella-Neto7, Ubiratan Fabres Machado8, Maria Lúcia Corrêa-Giannella1,9. 1. a Laboratório de Endocrinologia Celular e Molecular (LIM-25) , Faculdade de Medicina da Universidade de São Paulo (FMUSP) , Brazil ; 2. b Divisão de Oftalmologia , Hospital das Clínicas, FMUSP , Brazil ; 3. c Divisão de Endocrinologia , Hospital das Clínicas, FMUSP , Brazil ; 4. d Laboratório de Fisiologia Renal , Departamento de Fisiologia e Biofísica do Instituto de Ciências Biomédicas da Universidade de São Paulo (ICBUSP) , Brazil ; 5. e Divisão de Nefrologia , Hospital das Clínicas, FMUSP , Brazil ; 6. f Laboratório de Lípides (LIM-10) , FMUSP , Brazil ; 7. g Programa de Pós-Graduação em Medicina , Universidade Nove de Julho - UNINOVE , Brazil ; 8. h Laboratório de Metabolismo e Endocrinologia , Departamento de Fisiologia e Biofísica do ICBUSP , Brazil ; 9. i Núcleo de Terapia Celular e Molecular (NUCEL/NETCEM), FMUSP , Brazil.
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.
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.
Authors: Daniele P Santos-Bezerra; Luciano R Filgueiras; Maria Beatriz Monteiro; Sharon N Admoni; Ricardo V Perez; Ana M Cavaleiro; Cleide G Machado; Ubiratan F Machado; Marisa Passarelli; Sonia Jancar; Maria Lucia Correa-Giannella Journal: Mediators Inflamm Date: 2020-03-23 Impact factor: 4.711
Authors: Maria Beatriz Monteiro; Tatiana S Pelaes; Daniele P Santos-Bezerra; Karina Thieme; Antonio M Lerario; Sueli M Oba-Shinjo; Ubiratan F Machado; Marisa Passarelli; Suely K N Marie; Maria Lúcia Corrêa-Giannella Journal: Front Endocrinol (Lausanne) Date: 2020-04-30 Impact factor: 5.555