Epigenetics of kidney disease

Wanner, Nicola; Bechtel-Walz, Wibke

doi:10.1007/s00441-017-2588-x

Cited by 50 publications

(55 citation statements)

References 223 publications

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“…Small changes may lead to major consequences and result in cellular dysfunction or malignant outgrowth (Sun and Fang, 2016). Growing evidence suggests the epigenetic regulation of pro-inflammatory and pro-fibrotic gene expression, mediated by DNA methylation, histone modifications or microRNAs, is important in EMT and renal fibrogenesis (Wing et al, 2013;Rodriguez-Romo et al, 2015;Wanner and Bechtel-Walz, 2017;Lin and Wu, 2020).…”

Section: Epigenetic Regulation Of Pemt In the Kidneymentioning

confidence: 99%

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New Insights Into the Role and Mechanism of Partial Epithelial-Mesenchymal Transition in Kidney Fibrosis

2020

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Epithelial-mesenchymal transition (EMT) is described as the process in which injured renal tubular epithelial cells undergo a phenotype change, acquiring mesenchymal characteristics and morphing into fibroblasts. Initially, it was widely thought of as a critical mechanism of fibrogenesis underlying chronic kidney disease. However, evidence that renal tubular epithelial cells can cross the basement membrane and become fibroblasts in the renal interstitium is rare, leading to debate about the existence of EMT. Recent research has demonstrated that after injury, renal tubular epithelial cells acquire mesenchymal characteristics and the ability to produce a variety of profibrotic factors and cytokines, but remain attached to the basement membrane. On this basis, a new concept of "partial epithelial-mesenchymal transition (pEMT)" was proposed to explain the contribution of renal epithelial cells to renal fibrogenesis. In this review, we discuss the concept of pEMT and the most recent findings related to this process, including cell cycle arrest, metabolic alternation of epithelial cells, infiltration of immune cells, epigenetic regulation as well as the novel signaling pathways that mediate this disturbed epithelial-mesenchymal communication. A deeper understanding of the role and the mechanism of pEMT may help in developing novel therapies to prevent and halt fibrosis in kidney disease.

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Section: Epigenetic Regulation Of Pemt In the Kidneymentioning

confidence: 99%

“…DNA methylation occurs at the 50-position of the cytosine ring (5mC) within CpG dinucleotides of gene promotors (De Chiara and Crean, 2016;Wanner and Bechtel-Walz, 2017). It is catalyzed by DNA methyltransferases (DNMTs).…”

Section: Dna Methylationmentioning

confidence: 99%

New Insights Into the Role and Mechanism of Partial Epithelial-Mesenchymal Transition in Kidney Fibrosis

2020

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“…Epigenetics refers to the modulation of gene expression via post-translational modification of protein complexes associated with DNA, without changing the DNA sequence (16,17). Among the several protein/histone modifications are acetylation, methylation, phosphorylation, ubiquitination, and sumoylation (17,18). Protein methylation can occur in histone and nonhistone proteins and is induced by multiple histone lysine methyltransferases, including enhancer of zeste homolog 2 (EZH2).…”

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confidence: 99%

Targeting histone methyltransferase enhancer of zeste homolog‐2 inhibits renal epithelial‐mesenchymal transition and attenuates renal fibrosis

et al. 2018

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Enhancer of zeste homolog-2 (EZH2) is a methyltransferase that induces histone H3 lysine 27 trimethylation (H3K27me3) and functions as an oncogenic factor in many cancer types. Its role in renal epithelial-mesenchymal transition (EMT) remains unknown. In this study, we found that EZH2 and H3K27me3 were highly expressed in mouse kidney with unilateral ureteral obstruction and cultured mouse kidney proximal tubular (TKPT) cells undergoing EMT. Inhibition of EZH2 with 3-deazaneplanocin A (3-DZNeP) attenuated renal fibrosis, which was associated with preserving E-cadherin expression and inhibiting Vimentin up-regulation in the obstructed kidney. Treatment with 3-DZNeP or transfection of EZH2 siRNA also inhibited TGF-β1-induced EMT of TKPT cells. Injury to the kidney or cultured TKPT cells resulted in up-regulation of Snail-l family transcriptional repressor (Snail)-1 and Twist family basic helix-loop-helix (BHLH) transcription factor (Twist)-1, which are 2 transcription factors, and down-regulation of phosphatase and tensin homolog, a protein tyrosine phosphatase associated with inhibition of PI3K-protein kinase B (AKT) signaling; EZH2 inhibition or silencing reversed all those responses. 3-DZNeP was also effective in suppressing epithelial arrest at the G/M phase and dephosphorylating AKT and β-catenin in vivo and in vitro. These data indicate that EZH2 activation contributes to renal EMT and fibrosis through activation of multiple signaling pathways and suggest that EZH2 has potential as a therapeutic target for treatment of renal fibrosis.-Zhou, X., Xiong, C., Tolbert, E., Zhao, T. C., Bayliss, G., Zhuang, S. Targeting histone methyltransferase enhancer of zeste homolog-2 inhibits renal epithelial-mesenchymal transition and attenuates renal fibrosis.

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“…Activated DPP-4 phosphorylated integrin b1 complex triggers transforming growth factor-β (TGF-β) receptor dimerization and activation of vascular endothelial growth factor receptor Type 1 [36]. Hyperglycemia, free oxygen radicals, and proteinuria causes activation of NF-jB is within the diabetic kidney [37]. Activated NF-jB binds within the nucleus to the promoter regions of several genes that mediate the pathogenesis of DN like those encoding TGF-β1, chemokine ligand 2 also recognized as MCP-1 and intercellular adhesion molecule 1 [38].…”

Section: Discussionmentioning

confidence: 99%

Diabetic Nephropathy an Obvious Complication in Long Term Type 1 Diabetes Mellitus: A Case Study

Mohammad

Chigurupati

Othman

et al. 2017

Asian J Pharm Clin Res

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Most overwhelming complications of Type 1 diabetes mellitus patients are responsible for complications related to the microvascular system most likely with kidney. In the kidney, hyperglycemia induced microangiopathy resulting not only thickening of the glomerular capillary basement membrane but also to the proliferation of the mesangial matrix and solidifying of the tubular basement membrane. Several biochemical and pathological, factors are concerned for the development of diabetic renal microangiopathy. These include the glomerular hyperperfusion and hyperfiltration, transformed morphology of podocytes accompanies these basement membrane modifications, Type IV collagen augmented synthesis following the hyperglycemia, and increased expression of tissue matrix metalloproteinase. The aim of this case review is to highlight the recent advances in understanding the pathogenesis, diagnosis, the overview and the potential renoprotective therapeutic agents that would prevent the development or the progression of diabetic nephropathy.

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Epigenetics of kidney disease

Cited by 50 publications

References 223 publications

New Insights Into the Role and Mechanism of Partial Epithelial-Mesenchymal Transition in Kidney Fibrosis

New Insights Into the Role and Mechanism of Partial Epithelial-Mesenchymal Transition in Kidney Fibrosis

Targeting histone methyltransferase enhancer of zeste homolog‐2 inhibits renal epithelial‐mesenchymal transition and attenuates renal fibrosis

Diabetic Nephropathy an Obvious Complication in Long Term Type 1 Diabetes Mellitus: A Case Study

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