Are Alterations in DNA Methylation Related to CKD Development?

Rysz, Jacek; Franczyk, Beata; Rysz-Górzyńska, Magdalena; Gluba-Brzózka, Anna

doi:10.3390/ijms23137108

Cited by 6 publications

(2 citation statements)

References 116 publications

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“…DNA methylation is an epigenetic mechanism involving the transfer of methyl groups to the C5 site of cytosine to form 5-methylcytosine in mammalian genomes, 10 which is related to inflammation and fibrosis. 11 DNA methylate modification is regulated by methyltransferase and demethylase. 12 DNA methyltransferase 3A (DNMT3A) is a de novo methyltransferase necessary for mammalian development.…”

Section: Introductionmentioning

confidence: 99%

Endometriotic mesenchymal stem cells promote the fibrosis process of endometriosis through paracrine TGF‐β1 mediated RASAL1 inhibition

Feng,

Dong,

Tan

2023

J of Obstet and Gynaecol

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BackgroundEndometrial‐derived stem cells are key players in endometriosis (EMs) pathogenesis, while the mechanism involved is still unclear. Herein, the role and regulatory mechanism of endometriotic mesenchymal stem cells (ecto‐MSCs) in regulating fibrosis during EMs progression were investigated.MethodsThe mRNA and protein expressions were assessed using qRT‐PCR, western blot, and immunofluorescence. Flow cytometry was adopted to analyze the markers of MSCs. Transwell assay was adopted to examine endometriotic stromal cells (ESCs) migration and invasion. The interactions between DNMT3A and RASAL1 were analyzed by ChIP assay. In addition, MSP was employed to detect RASAL1 promoter methylation level.ResultsEcto‐MSCs promoted ESCs migration, invasion, and fibrosis process by TGF‐β1 paracrine. It was subsequently revealed that TGF‐β1 upregulated DNMT3A in ESCs in a SMAD3‐dependent manner. As expected, DNMT3A knockdown abolished ecto‐MSCs' facilitation on ESCs migration, invasion, and fibrosis process. DNMT3A, as a methyltransferase, reduced RASAL1 expression in TGF‐β1‐treated ESCs by increasing RASAL1 promoter methylation level. RASAL1, as an antifibrotic protein, was lowly expressed in TGF‐β1‐treated ESCs, and its overexpression ameliorated TGF‐β1‐induced increase in ESCs migration, invasion, and fibrosis process.ConclusionTGF‐β1 secreted by ecto‐MSCs facilitated fibrogenesis in EMs through SMAD3/DNMT3A‐mediated RASAL1 inhibition.

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Section: Introductionmentioning

confidence: 99%

Endometriotic mesenchymal stem cells promote the fibrosis process of endometriosis through paracrine TGF‐β1 mediated RASAL1 inhibition

Feng,

Dong,

Tan

2023

J of Obstet and Gynaecol

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“…Remarkably, renal methylation signatures also accurately reflect the presence of kidney cancer, with the methylome of RCC cells exhibiting a significantly older biological age, a phenomena seen in a wide range of cancers. Moreover, it has been shown that specific DNA methylation signatures predict various clinical outcomes, and correlate with renal function (Lu et al 2019; Dritsoula et al 2021; Rysz et al 2022; Schlosser et al 2021).…”

Section: Introductionmentioning

confidence: 99%

Kidney-specific methylation patterns correlate with kidney function and are lost upon kidney disease progression

Sagy

Meyrom

Beckerman

et al. 2022

Preprint

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Chronological and biological age correlate with DNA methylation levels at specific sites in the genome. Linear combinations of multiple methylation sites, termed epigenetic clocks, can inform us of the chronological age and predict multiple health-related outcomes. However, why some sites correlate with lifespan, healthspan, or specific medical conditions remains poorly understood. Kidney fibrosis is the common pathway for Chronic Kidney Disease (CKD) which affects 10% of Europe and USA population. Currently estimated glomerular filtration rate (eGFR) is the common diagnostic measure. Here we identify epigenetic clocks and methylation sites that correlate with kidney function. Moreover, we identify methylation sites that have a unique methylation signature in the kidney. Methylation levels in the majority of these sites correlates with kidney state and function. When kidney function deteriorates, as measured by interstitial fibrosis (IF) on kidney biopsy and by eGFR, all of these sites regress towards the common methylation pattern observed in other tissues. Interestingly, while the majority of sites are less methylated in the kidney and become more methylated with loss of function, a fraction of the sites are highly methylated in the kidney and become less methylated when kidney function declines. These methylation sites are enriched for specific transcription factor binding sites. In a large subset of sites, changes in methylation pattern are accompanied by changes in gene expression in kidneys of chronic kidney disease patients. These results support the information theory of aging, and the hypothesis that the unique tissue identity, as captured by methylation patterns, is lost as tissue function declines. However, this information loss is not random, but guided towards a baseline that is dependent on the genomic loci.

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