Monteiro Maria Beatriz, Santos-Bezerra Daniele Pereira, Thieme Karina, Admoni Sharon Nina, Perez Ricardo Vessoni, Machado Cleide Guimarães, Queiroz Marcia Silva, Nery Marcia, Oliveira-Souza Maria, Woronik Viktoria, Passarelli Marisa, Giannella-Neto Daniel, Machado Ubiratan Fabres, Corrêa-Giannella Maria Lúcia
a Laboratório de Endocrinologia Celular e Molecular (LIM-25) , Faculdade de Medicina da Universidade de São Paulo (FMUSP) , Brazil ;
b Divisão de Oftalmologia , Hospital das Clínicas, FMUSP , Brazil ;
Free Radic Res. 2016;50(1):101-10. doi: 10.3109/10715762.2015.1109083. Epub 2015 Nov 30.
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.
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.
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.
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.
硫氧还蛋白相互作用蛋白（TXNIP）是抗氧化剂硫氧还蛋白（Trx）的一种抑制剂，在高血糖情况下表达上调，并与糖尿病并发症的发病机制有关。我们评估了不同程度慢性并发症的1型糖尿病（T1D）患者尿沉渣及外周血单核细胞（PBMC）中编码TXNIP和Trx（TXN）的基因的mRNA表达。
采用qPCR定量检测按是否存在糖尿病肾病（DN）、视网膜病变、周围神经病变及心血管神经病变分类的患者尿沉渣（n = 55）及PBMC（n = 161）中的靶基因；还纳入了26名健康对照者及13名患有非糖尿病肾病（局灶节段性肾小球硬化，FSGS）的患者。
关于尿沉渣，与对照组相比，T1D患者（p = 0.0023）及FSGS患者（p = 0.0027）中TXNIP（而非TXN）的表达更高。有DN与无DN的T1D患者中，TXNIP和TXN的表达分别更高（p = 0.032）；估计肾小球滤过率（eGFR）<60与≥60 mL/min/1.73 m²的T1D患者中，TXNIP和TXN的表达分别更高（p = 0.008）。eGFR与TXNIP（p = 0.04，r = -0.28）及TXN（p = 0.04，r = -0.30）的表达呈负相关。在24个月的中位随访后，每年eGFR下降≥5 mL/min/1.73 m²的T1D患者的基础TXNIP表达高于每年下降<5 mL/min/1.73 m²的患者。T1D患者PBMC中的TXNIP（p < 0.0001）及TXN（p = 0.002）表达显著高于对照组，但有或无慢性并发症的患者之间未观察到差异。
TXNIP和TXN在患有糖尿病肾病（DKD）的T1D患者的尿沉渣中上调，但只有TXNIP的表达与eGFR下降幅度相关。
