A novel biomarker for acute kidney injury using TaqMan-based unmethylated DNA-specific polymerase chain reaction

Endo, Kazuhira; Kito, Naoko; Fukushima, Yasue; Weng, Huachun; Iwai, Naoharu

doi:10.2220/biomedres.35.207

Cited by 10 publications

(7 citation statements)

References 22 publications

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“…DNA was bisulfite-converted using a MethylEdge Bisulfite Conversion System (Promega, WI, USA), following the manufacturer's recommendations. Fragments including the target site were PCR-amplified from the bisulfite-converted DNA using primer sets ( Table 1 ) with EpiTaq HS DNA polymerase (TAKARA, Shiga, Japan) as described previously [ 15 ]. The PCR product was cloned into the pTA2 vector using a TArget Clone Plus cloning kit (TOYOBO, Osaka, Japan).…”

Section: Methodsmentioning

confidence: 99%

Establishment of the MethyLight Assay for Assessing Aging, Cigarette Smoking, and Alcohol Consumption

Endo

Nakanishi

et al. 2015

BioMed Research International

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The environmental factors such as aging, smoking, and alcohol consumption have been reported to influence DNA methylation (DNAm). However, the versatility of DNAm measurement by DNAm array systems is low in clinical use. Thus, we developed the MethyLight assay as a simple method to measure DNAm. In the present study, we isolated peripheral blood DNA from 33 healthy volunteers and selected cg25809905, cg02228185, and cg17861230 as aging, cg23576855 as smoking, and cg02583484 as alcohol consumption biomarkers. The predicted age by methylation rates of cg25809905 and cg17861230 significantly correlated with chronological age. In immortalized B-cells, DNAm rates of two sites showed a younger status than the chronological age of donor. On the other hand, the predicted age of the patients with myocardial infarction (MI) was not accelerated. The methylation rate of cg23576855 was able to discriminate the groups based on the smoking status. The DNAm rate of cg02583484 was reduced in subjects with habitual alcohol consumption compared to that of subjects without habitual alcohol consumption. In conclusion, our MethyLight assay system reconfirms that aging, smoking, and alcohol consumption influenced DNAm in peripheral blood in the Japanese. This MethyLight system will facilitate DNAm measurement in epidemiological and clinical studies.

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Section: Methodsmentioning

confidence: 99%

Establishment of the MethyLight Assay for Assessing Aging, Cigarette Smoking, and Alcohol Consumption

Endo

Nakanishi

et al. 2015

BioMed Research International

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“…Circulating or urinary microRNAs are being evaluated (92), and kidney-specific DNA methylation patterns are also being analyzed (93). Recent attention has also focused on urinary extracellular vesicles (94), which contain mRNA, microRNA, and proteins reflective of cellular physiology and pathophysiology along the nephron.…”

Section: Biomarkersmentioning

confidence: 99%

Acute Kidney Injury

2016

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Acute kidney injury (AKI) is a global public health concern associated with high morbidity, mortality, and healthcare costs. Other than dialysis, no therapeutic interventions reliably improve survival, limit injury, or speed recovery. Despite recognized shortcomings of in vivo animal models, the underlying pathophysiology of AKI and its consequence, chronic kidney disease (CKD), is rich with biological targets. We review recent findings relating to the renal vasculature and cellular stress responses, primarily the intersection of the unfolded protein response, mitochondrial dysfunction, autophagy, and the innate immune response. Maladaptive repair mechanisms that persist following the acute phase promote inflammation and fibrosis in the chronic phase. Here macrophages, growth-arrested tubular epithelial cells, the endothelium, and surrounding pericytes are key players in the progression to chronic disease. Better understanding of these complex interacting pathophysiological mechanisms, their relative importance in humans, and the utility of biomarkers will lead to therapeutic strategies to prevent and treat AKI or impede progression to CKD or end-stage renal disease (ESRD).

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“…Furthermore, there was a trend toward increased aberrant hypermethylation of urine CALCA in patients with biopsy-proven acute tubular necrosis versus acute rejection and slow or prompt graft function [28]. Plasma levels of unmethylated DNA corresponding to the Slc22a12 promoter region, a urate transporter specifically expressed in proximal tubular cells, were undetectable at baseline and were significantly elevated after acute kidney cortex necrosis [29]. Methylation of promoter kallikrein (KLK1) CpG in the kidney was higher in blood than urine DNA, while KLK1 methylation in blood DNA was higher in established AKI than healthy controls, though KLK1 methylation in urine tended to be elevated in AKI, directionally consistent with earlier/incipient but not later/established changes in KLK1 excretion in AKI [30].…”

Section: Methylation and Acute Kidney Injurymentioning

confidence: 99%

Epigenetics in acute kidney injury

Tang¹,

Zhuang²

2015

Current Opinion in Nephrology and Hypertension

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Purpose of review Recent advances in epigenetics indicate the involvement of several epigenetic modifications in the pathogenesis of acute kidney injury (AKI). The purpose of this review is to summarize our understanding of recent advances in epigenetic regulation of AKI and provide mechanistic insight into the role of acetylation, methylation, and microRNA expression in the pathological processes of AKI. Recent findings Enhancement of protein acetylation by pharmacological inhibition of histone deacetylases (HDACs) leads to more severe tubular injury and impairment of renal structural and functional recovery. The changes in promoter DNA methylation occur in the kidney with ischemia/reperfusion. microRNA expression is associated with regulation of both renal injury and regeneration after AKI. Summary Recent studies on epigenetic regulation indicate that acetylation, methylation, and microRNA expression are critically implicated in the pathogenesis of AKI. Strategies targeting epigenetic processes may hold a therapeutic potential for patients with AKI.

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A novel biomarker for acute kidney injury using TaqMan-based unmethylated DNA-specific polymerase chain reaction

Cited by 10 publications

References 22 publications

Establishment of the MethyLight Assay for Assessing Aging, Cigarette Smoking, and Alcohol Consumption

Establishment of the MethyLight Assay for Assessing Aging, Cigarette Smoking, and Alcohol Consumption

Acute Kidney Injury

Epigenetics in acute kidney injury

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