Metabolic memory and diabetic nephropathy: Beneficial effects of natural epigenetic modifiers

Kushwaha, Kriti; Sharma, Sandeep; Gupta, Jeena

doi:10.1016/j.biochi.2020.01.007

Cited by 22 publications

(14 citation statements)

References 171 publications

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“…Yet, despite the significant advances in clinical and experimental research in diabetes and its complications, the diagnosis and effective treatment of DKD remains challenging [ 4 , 5 , 6 , 7 , 8 ]. Noteworthy, due to the metabolic memory in diabetes (an emergent and rapidly evolving epigenetic-related mechanistic concept) and in spite of the therapeutic control of hyperglycaemia, diabetes pathological long-lasting effects persist and continue to promote systemic cellular detrimental effects [ 44 , 45 , 46 , 47 ]. Consequently, in order to efficiently counteract/attenuate the diabetes-accelerated renal failure, other intrinsic glomerular cell-specific signalling pathways should be considered for drug targeting.…”

Section: Discussionmentioning

confidence: 99%

Activated Histone Acetyltransferase p300/CBP-Related Signalling Pathways Mediate Up-Regulation of NADPH Oxidase, Inflammation, and Fibrosis in Diabetic Kidney

et al. 2021

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Accumulating evidence implicates the histone acetylation-based epigenetic mechanisms in the pathoetiology of diabetes-associated micro-/macrovascular complications. Diabetic kidney disease (DKD) is a progressive chronic inflammatory microvascular disorder ultimately leading to glomerulosclerosis and kidney failure. We hypothesized that histone acetyltransferase p300/CBP may be involved in mediating diabetes-accelerated renal damage. In this study, we aimed at investigating the potential role of p300/CBP in the up-regulation of renal NADPH oxidase (Nox), reactive oxygen species (ROS) production, inflammation, and fibrosis in diabetic mice. Diabetic C57BL/6J mice were randomized to receive 10 mg/kg C646, a selective p300/CBP inhibitor, or its vehicle for 4 weeks. We found that in the kidney of C646-treated diabetic mice, the level of H3K27ac, an epigenetic mark of active gene expression, was significantly reduced. Pharmacological inhibition of p300/CBP significantly down-regulated the diabetes-induced enhanced expression of Nox subtypes, pro-inflammatory, and pro-fibrotic molecules in the kidney of mice, and the glomerular ROS overproduction. Our study provides evidence that the activation of p300/CBP enhances ROS production, potentially generated by up-regulated Nox, inflammation, and the production of extracellular matrix proteins in the diabetic kidney. The data suggest that p300/CBP-pharmacological inhibitors may be attractive tools to modulate diabetes-associated pathological processes to efficiently reduce the burden of DKD.

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Section: Discussionmentioning

confidence: 99%

Activated Histone Acetyltransferase p300/CBP-Related Signalling Pathways Mediate Up-Regulation of NADPH Oxidase, Inflammation, and Fibrosis in Diabetic Kidney

et al. 2021

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“…RAGE -трансмембранный белок, который экспрессируется в большом количестве клеток, таких как макрофаги, эндотелиальные клетки, нейроны, а также канальцевые и клубочковые эпителиальные клетки в почках [1]. Поскольку накопление AGE и активация RAGE вызывают в том числе эпигенетические изменения, которые индуцируют экспрессию различных генов в клетках и активируют воспаление, повреждение тканей, предполагается, что ось AGE-RAGE играет центральную роль в феномене метаболической памяти, значение которого в прогрессировании и развитии диабетических осложнений подтверждено в исследовании DCCT/EDIC [28,[31][32][33][34].…”

Section: роль взаимодействия Age с Rage в развитии диабетической нефр...unclassified

The role of advanced glycation end products in patogenesis of diabetic nephropathy

et al. 2022

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Diabetes mellitus (DM) and chronic kidney disease are the diseases that have exceeded epidemic thresholds in terms of prevalence all over the world. That made it possible to classify them as non-communicable epidemics of the XXI century. Diabetic nephropathy (DN) is implicated with high levels of disablement and mortality. Advanced glycation end products (AGE) play a key role in the progression of DN. Increased formation of AGE occurs due to hyperglycemia under the conditions of diabetes. Moreover, there are additional factors in DN that increase the elaboration of AGE, such as high levels of oxidative stress and decreased renal clearance which slows down the AGE excretion. Both immediate effects of AGE and interaction of AGE with its cell-bound receptor (RAGE) result in a сascade of events that lead to further progression of DN. Thus, the research of the new therapeutic approaches targeted on the AGE-RAGE system is of great interest to slow progression of DN and improve the prognosis.

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“…Excessive accumulation of glucose and lipids are the initial inducers of DN. The consequent induction of inflammation, fibrosis, hemodynamic alterations, oxidative stress, and apoptosis are the main pathogenic characteristics of DN ( Barrera-Chimal and Jaisser, 2020 ; Kushwaha et al, 2020 ; Opazo-Ríos et al, 2020 ; Thongnak et al, 2020 ), but there is emerging evidence that additional signaling molecules function in the pathogenesis of DN. These include renal endothelial-related molecules (endothelial sirtuin 3 [SIRT3] ( Wang et al, 2019c ), endothelial glucocorticoid receptors [E-GRs] ( Srivastava et al, 2021a ), and endothelial fibroblast growth factor receptor 1 [FGFR1]) ( Typiak et al, 2021 ), and the podocyte-glucocorticoid receptor (P-GR) ( Srivastava et al, 2021b ).…”

Section: Gsdms and Gsdmementioning

confidence: 99%

Mini-Review: GSDME-Mediated Pyroptosis in Diabetic Nephropathy

Sun

Zhou

et al. 2021

Front. Pharmacol.

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Pyroptosis is a recently identified type of lytic programmed cell death, in which pores form in the plasma membrane, and cells swell, rupture, and then release their contents, including inflammatory cytokines. Molecular studies indicated that pyroptosis may occur via a gasdermin D (GSDMD) and caspase-1 (Casp1) -dependent classical pathway, a GSDMD and Casp11/4/5-dependent non-classical pathway, or a gasdermin E (GSDME) and Casp3-dependent pathway. Studies of animal models and humans indicated that pyroptosis can exacerbate several complications of diabetes, including diabetic nephropathy (DN), a serious microvascular complication of diabetes. Many studies investigated the mechanism mediating the renoprotective effect of GSDMD regulation in the kidneys of patients and animal models with diabetes. As a newly discovered regulatory mechanism, GSDME and Casp3-dependent pyroptotic pathway in the progression of DN has also attracted people’s attention. Z-DEVD-FMK, an inhibitor of Casp3, ameliorates albuminuria, improves renal function, and reduces tubulointerstitial fibrosis in diabetic mice, and these effects are associated with the inhibition of GSDME. Studies of HK-2 cells indicated that the molecular and histological features of secondary necrosis were present following glucose stimulation due to GSDME cleavage, such as cell swelling, and release of cellular contents. Therefore, therapies targeting Casp3/GSDME-dependent pyroptosis have potential for treatment of DN. A novel nephroprotective strategy that employs GSDME-derived peptides which are directed against Casp3-induced cell death may be a key breakthrough. This mini-review describes the discovery and history of research in this pyroptosis pathway and reviews the function of proteins in the gasdermin family, with a focus on the role of GSDME-mediated pyroptosis in DN. Many studies have investigated the impact of GSDME-mediated pyroptosis in kidney diseases, and these studies used multiple interventions, in vitro models, and in vivo models. We expect that further research on the function of GDSME in DN may provide valuable insights that may help to improve treatments for this disease.

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Metabolic memory and diabetic nephropathy: Beneficial effects of natural epigenetic modifiers

Cited by 22 publications

References 171 publications

Activated Histone Acetyltransferase p300/CBP-Related Signalling Pathways Mediate Up-Regulation of NADPH Oxidase, Inflammation, and Fibrosis in Diabetic Kidney

Activated Histone Acetyltransferase p300/CBP-Related Signalling Pathways Mediate Up-Regulation of NADPH Oxidase, Inflammation, and Fibrosis in Diabetic Kidney

The role of advanced glycation end products in patogenesis of diabetic nephropathy

Mini-Review: GSDME-Mediated Pyroptosis in Diabetic Nephropathy

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