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

Monteiro, Maria Beatriz; Santos‐Bezerra, Daniele Pereira; Thieme, Karina; Admoni, Sharon Nina; Perez, Ricardo Vessoni; Machado, Cleide Guimarães; Queiroz, Márcia Silva; Nery, Márcia; Oliveira‐Souza, Maria; Woronik, Viktoria; Passarelli, Marisa; Giannella-Neto, Daniel; Machado, Ubiratan Fabres; Corrêa-Giannella, Maria Lúcia

doi:10.3109/10715762.2015.1109083

Cited by 23 publications

(22 citation statements)

References 34 publications

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“…Participants. One hundred and sixty-four T1D individuals were enrolled in this cross-sectional study ( All T1D participants were evaluated for the presence of the following chronic microvascular complications: diabetic retinopathy (DR), diabetes kidney disease (DKD), peripheral neuropathy, and cardiovascular autonomic neuropathy (CAN), as previously described [14].…”

Section: Methodsmentioning

confidence: 99%

Leukotriene Pathway Activation Associates with Poor Glycemic Control and with Cardiovascular Autonomic Neuropathy in Type 1 Diabetes

Santos‐Bezerra

Filgueiras

Monteiro

et al. 2020

Mediators of Inflammation

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Background and Aims. Since hyperglycemia promotes inflammation by different pathways and inflammation participates in the development of chronic diabetes complications, we investigated the association between the leukotriene (LT) pathway and microvascular diabetes complications. Methods and Results. Quantitative polymerase chain reaction was employed to quantify the expression of ALOX5 (encodes 5-lipoxygenase), LTB4R (encodes one of the LTB4 receptors), and MYD88 in peripheral blood mononuclear cells from 164 type 1 diabetes (T1D) individuals presenting or not diabetes kidney disease, retinopathy, peripheral neuropathy, and cardiovascular autonomic neuropathy (CAN); 26 nondiabetic subjects were included as controls. LTB4 plasmatic concentrations were also evaluated. The expression of LTB4R was significantly higher in T1D individuals than in controls. T1D individuals with microvascular complications presented lower MYD88 mRNA expression when compared to those without microvascular complications. Higher LTB4 concentrations were found in individuals with CAN versus without CAN. The observation of two distinct subgroups of T1D individuals in the correlation analyses motivated us to evaluate the characteristics of each one of these groups separately. The group presenting higher expression of ALOX5 and of LTB4R also presented higher values of HbA1C, of fructosamine, and of plasmatic LTB4. Conclusion. In the diabetes setting, the LT pathway is not only activated by hyperglycemia but is also modulated by the status of the autonomic nervous system.

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Section: Methodsmentioning

confidence: 99%

Leukotriene Pathway Activation Associates with Poor Glycemic Control and with Cardiovascular Autonomic Neuropathy in Type 1 Diabetes

Santos‐Bezerra

Filgueiras

Monteiro

et al. 2020

Mediators of Inflammation

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“…Moreover, TXNIP is one of the mediators of oxidative stress‐induced β‐cell (cells that tightly associated with diabetes and insulin secretion) glucotoxicity, which has been proved to regulate miRNA expression in β‐cells, β‐cell function, and insulin content . It has been clarified that TXNIP participated in human diseases, including type 1 diabetes, type 2 diabetes mellitus, and DR . However, the target relation between miR‐20b‐3p and TXNIP has not been uncovered yet.…”

Section: Introductionmentioning

confidence: 99%

Elevated microRNA‐20b‐3p and reduced thioredoxin‐interacting protein ameliorate diabetic retinopathy progression by suppressing the NLRP3 inflammasomes

Wang

et al. 2020

IUBMB Life

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Over the years, microRNA‐20b‐3p (miR‐20b‐3p) has been found to play an essential role in human diseases; we aimed to investigate the effect of miR‐20b‐3p on the progression of diabetic retinopathy (DR). The DR rat models were established by streptozotocin injection and treated with miR‐20b‐3p mimics, silenced, or overexpressed thioredoxin‐interacting protein (TXNIP). Afterward, the expression of miR‐20b‐3p and TXNIP, visual function, inflammatory factors, microvascular injury, vascular permeability, cell apoptosis, and angiogenesis in rats' retinal tissues were assessed. The target relation between miR‐20b‐3p and TXNIP was confirmed by dual luciferase reporter gene assay. MiR‐20b‐3p was poorly expressed while TXNIP was highly expressed in DR rats' retinal tissues. Elevated miR‐20b‐3p and inhibited TXNIP promoted the visual function, and restricted the inflammatory reaction, microvascular injury, vascular permeability, cell apoptosis, and angiogenesis in DR rats, thereby decelerating the development of DR. Furthermore, TXNIP was targeted by miR‐20b‐3p. We have found in this study that elevated miR‐20b‐3p could repress the levels of inflammatory factors by inhibiting TXNIP, thus attenuating the pathology of retina in DR rats, which provided new candidates for DR treatment.

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“…The antioxidant TRX is inhibited by thioredoxininteracting protein (TXNIP) both of which have been shown to be upregulated in urine and peripheral blood mononuclear cells (PBMCs) from T1D patients with DN. 72 In this setting, only TXNIP expression correlated with GFR decline. Interestingly, the angiotensin (Ang)II receptor blocker, telmisartan, demonstrated reno-protection in a T2D rat model by improving oxidative stress through the downregulation of TXNIP.…”

Section: Diabetic Nephropathy Antioxidant Defences and Immunotherapiesmentioning

confidence: 85%

“…The antioxidant TRX is inhibited by thioredoxin‐interacting protein (TXNIP) both of which have been shown to be upregulated in urine and peripheral blood mononuclear cells (PBMCs) from T1D patients with DN 72. In this setting, only TXNIP expression correlated with GFR decline.…”

Section: Diabetic Nephropathy Antioxidant Defences and Immunotherapiesmentioning

confidence: 99%

Recent novel approaches to limit oxidative stress and inflammation in diabetic complications

et al. 2018

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Diabetes is considered a major burden on the healthcare system of Western and non‐Western societies with the disease reaching epidemic proportions globally. Diabetic patients are highly susceptible to developing micro‐ and macrovascular complications, which contribute significantly to morbidity and mortality rates. Over the past decade, a plethora of research has demonstrated that oxidative stress and inflammation are intricately linked and significant drivers of these diabetic complications. Thus, the focus now has been towards specific mechanism‐based strategies that can target both oxidative stress and inflammatory pathways to improve the outcome of disease burden. This review will focus on the mechanisms that drive these diabetic complications and the feasibility of emerging new therapies to combat oxidative stress and inflammation in the diabetic milieu.

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

Abstract: 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.

Cited by 23 publications

References 34 publications

Leukotriene Pathway Activation Associates with Poor Glycemic Control and with Cardiovascular Autonomic Neuropathy in Type 1 Diabetes

Leukotriene Pathway Activation Associates with Poor Glycemic Control and with Cardiovascular Autonomic Neuropathy in Type 1 Diabetes

Elevated microRNA‐20b‐3p and reduced thioredoxin‐interacting protein ameliorate diabetic retinopathy progression by suppressing the NLRP3 inflammasomes

Recent novel approaches to limit oxidative stress and inflammation in diabetic complications

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