Chronic advanced-glycation end products treatment induces TXNIP expression and epigenetic changes in glomerular podocytes in vivo and in vitro

Thieme, Karina; Pereira, Beatriz Maria Veloso; Silva, Karolline S. da; Fabre, N.; Catanozi, Sérgio; Passarelli, Marisa; Côrrea-Giannella, Maria Lúcia

doi:10.1016/j.lfs.2020.118997

Cited by 8 publications

(6 citation statements)

References 33 publications

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“…Moreover, the role of TXNIP in glomerular injury was verified by the direct interaction found between TXNIP and NRLP3 inflammasome activation in cultured human podocytes (18). In response to advanced-glycation end products, compounds resulting from the process of ageing as well as inflammation and hyperglycemia, TXNIP was highly expressed in glomerulus and podocyte, where the epigenetic machinery of pos-translational histone modifications are reported to be regulators of TXNIP expression under hyperglycemia and advanced-glycation products exposure (19). In the context of FSGS patients, increased TXNIP level was detected in urinary sediments when compared to healthy individuals, while the same occur in diabetic nephropathy patients (20).…”

Section: Txnip As An Inflammation Componentmentioning

confidence: 87%

Thioredoxin-Interacting Protein: The Redoxissome Complex in Glomerular Lesion

Pereira¹,

Santos²,

Barbosa³

et al. 2022

ejb

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Chronic kidney disease (CKD) is estimated to affect roughly 13.4% of the world's population (1). Damage to renal tissue can occur from different underlying conditions and mechanisms, including infections, hemodynamic changes, and direct injury to renal components.Glomeruli damage currently accounts for 25% of the total kidney lesions observed in the adult population, with a higher incidence among the young population (2).Focal Segmentar Glomerulosclerosis (FSGS) is a histologic pattern of lesion of the glomeruli characterized by the focal manifestation of sclerotic lesions in some glomeruli, and segmental fibrosis observed in portions

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Section: Txnip As An Inflammation Componentmentioning

confidence: 87%

Thioredoxin-Interacting Protein: The Redoxissome Complex in Glomerular Lesion

Pereira¹,

Santos²,

Barbosa³

et al. 2022

ejb

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“…Siddiqi et al [ 42 ] showed that depletion of EZH2 and, consequently, reduced H3K27me3 in diabetic rats induces podocyte injury, oxidative stress and proteinuria [ 42 ]. Other findings describe an overall reduced H3K27 trimethylation in the kidneys of high-fat-fed rats which goes along with the metabolic memory [ 43 ], in diabetic mouse models [ 44 , 45 , 46 , 47 , 48 ] or in nephrotic patients [ 49 , 50 ]. However, there are also conflicting studies.…”

Section: Discussionmentioning

confidence: 99%

The Role of Hypoxia on the Trimethylation of H3K27 in Podocytes

Barth,

Loeffler,

Bondeva

et al. 2023

Biomedicines

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Epigenetic alterations contribute to the pathogenesis of chronic diseases such as diabetes mellitus. Previous studies of our group showed that diabetic conditions reduce the trimethylation of H3K27 in podocytes in a NIPP1- (nuclear inhibitor of protein phosphatase 1) and EZH2- (enhancer of zeste homolog 2) dependent manner. It has been previously reported that in differentiated podocytes, hypoxia decreases the expression of slit diaphragm proteins and promotes foot process effacement, thereby contributing to the progression of renal disease. The exact mechanisms are, however, not completely understood. The aim of this study was to analyze the role of hypoxia and HIFs (hypoxia-inducible factor) on epigenetic changes in podocytes affecting NIPP1, EZH2 and H3K27me3, in vitro and in vivo. In vivo studies were performed with mice exposed to 10% systemic hypoxia for 3 days or injected with 3,4-DHB (dihydroxybenzoate), a PHD (prolyl hydroxylase) inhibitor, 24 h prior analyses. Immunodetection of H3K27me3, NIPP1 and EZH2 in glomerular podocytes revealed, to the best of our knowledge for the first time, that hypoxic conditions and pharmacological HIFs activation significantly reduce the expression of NIPP1 and EZH2 and diminish H3K27 trimethylation. These findings are also supported by in vitro studies using murine-differentiated podocytes.

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“…For immunofluorescence studies, kidney slices were deparaffinized and submitted to antigenic retrieval with EDTA buffer (1mM EDTA, 0.05% Tween 20, pH 8) ( 19 , 20 ). After blocking (Protein Block, DAKO Agilent Technologies Inc., Saint Clair, CA USA) for 1 hour, sections were incubated overnight at 4° C using the following primary antibodies: mouse anti-collagen IV (1:400, Abcam, Cambridge, UK); rabbit anti-TET1 (1:150, Genetex, Radnor, PA USA); rabbit anti-TET3 (1:100, Novus Biotechnology, Centennial, CO USA); and rabbit anti-Wilms’ tumor suppressor 1 (WT1) (1:200, Novus Biotechnology).…”

Section: Methodsmentioning

confidence: 99%

DNA methylation enzymes in the kidneys of male and female BTBR ob/ob mice

et al. 2023

Self Cite

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Diabetic kidney disease (DKD) is the leading cause of the end-stage renal disease. Recent studies have shown that epigenetic modifications contribute to alterations in gene expression and the development of DKD. This study aimed to show an expression profile of key DNA (de)methylation enzymes (DNMT, TET proteins) and their differences between sexes under obesity and diabetic condition. Male and female black and tan brachyury (BTBR) ob/ob mice and their corresponding wild-type littermates (BTBR WT) were studied until 16 weeks of age. Metabolic parameters, kidney morphophysiology and the expression of fibrotic markers and epigenetic enzymes were studied in whole kidney tissue or specifically in the glomerulus. The results showed sexual dimorphism in the development of metabolic disease and in kidney morphophysiology. Female mice have a different profile of DNMTs expression in both WT and obese/diabetic condition. Furthermore, metabolic condition negatively modulated the glomerular expression of TET1 and TET3 only in females. To our knowledge, this is the first study that shows a kidney profile of the expression of key (de)methylation enzymes, DNMTs and TETs, in the BTBR ob/ob experimental model of DKD and its association with sex. The knowledge of this epigenetic profile may help future research to understand the pathophysiology of DKD in males and females.

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Chronic advanced-glycation end products treatment induces TXNIP expression and epigenetic changes in glomerular podocytes in vivo and in vitro

Cited by 8 publications

References 33 publications

Thioredoxin-Interacting Protein: The Redoxissome Complex in Glomerular Lesion

Thioredoxin-Interacting Protein: The Redoxissome Complex in Glomerular Lesion

The Role of Hypoxia on the Trimethylation of H3K27 in Podocytes

DNA methylation enzymes in the kidneys of male and female BTBR ob/ob mice

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