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epigenetics in CKD

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https://www.readbyqxmd.com/read/28489601/cellular-senescence-senescence-associated-secretory-phenotype-and-chronic-kidney-disease
#1
REVIEW
Wen-Juan Wang, Guang-Yan Cai, Xiang-Mei Chen
Chronic kidney disease (CKD) is increasingly being accepted as a type of renal ageing. The kidney undergoes age-related alterations in both structure and function. To date, a comprehensive analysis of cellular senescence and senescence-associated secretory phenotype (SASP) in CKD is lacking. Hence, this review mainly discusses the relationship between the two phenomena to show the striking similarities between SASP and CKD-associated secretory phenotype (CASP). It has been reported that replicative senescence, stress-induced premature ageing, and epigenetic abnormalities participate in the occurrence and development of CKD...
April 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28487070/noncoding-rna-and-epigenetic-gene-regulation-in-renal-disease
#2
REVIEW
Satya K Kota, Savithri B Kota
Kidneys have a major role in normal physiology and metabolic homeostasis. Loss or impairment of kidney function is a common occurrence in several metabolic disorders, including hypertension and diabetes. Chronic kidney disease (CKD) affect nearly 10% of the population worldwide; ranks 18th in the list of causes of death; and contributes to a significant proportion of healthcare costs. The tissue repair and regenerative potential of kidneys are limited and they decline during aging. Recent studies have demonstrated a key role for epigenetic processes and players, such as DNA methylation, histone modifications, noncoding (nc)RNA, and so on, in both kidney development and disease...
May 6, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28468297/hypoxia-hif-and-associated-signaling-networks-in-chronic-kidney-disease
#3
REVIEW
Jing Liu, Qingqing Wei, Chunyuan Guo, Guie Dong, Yu Liu, Chengyuan Tang, Zheng Dong
The pathogenesis of chronic kidney disease (CKD) is complex and apparently multifactorial. Hypoxia or decrease in oxygen supply in kidney tissues has been implicated in CKD. Hypoxia inducible factors (HIF) are a small family of transcription factors that are mainly responsive to hypoxia and mediate hypoxic response. HIF plays a critical role in renal fibrosis during CKD through the modulation of gene transcription, crosstalk with multiple signaling pathways, epithelial-mesenchymal transition, and epigenetic regulation...
April 30, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28285987/tgf%C3%AE-incurred-epigenetic-aberrations-of-mirna-and-dna-methyltransferase-suppress-klotho-and-potentiate-renal-fibrosis
#4
Shasha Yin, Qin Zhang, Jun Yang, Wenjun Lin, Yanning Li, Fang Chen, Wangsen Cao
Renal fibrosis is a common pathological feature of chronic kidney diseases (CKD) and its development and progression are significantly affected by epigenetic modifications such as aberrant miRNA and DNA methylation. Klotho is an anti-aging and anti-fibrotic protein and its early decline after renal injury is reportedly associated with aberrant DNA methylation. However, the key upstream pathological mediators and the molecular cascade leading to epigenetic Klotho suppression are not exclusively established. Here we investigate the epigenetic mechanism of Klotho deficiency and its functional relevance in renal fibrogenesis...
March 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28228736/stress-signal-network-between-hypoxia-and-er-stress-in-chronic-kidney-disease
#5
REVIEW
Hiroshi Maekawa, Reiko Inagi
Chronic kidney disease (CKD) is characterized by an irreversible decrease in kidney function and induction of various metabolic dysfunctions. Accumulated findings reveal that chronic hypoxic stress and endoplasmic reticulum (ER) stress are involved in a range of pathogenic conditions, including the progression of CKD. Because of the presence of an arteriovenous oxygen shunt, the kidney is thought to be susceptible to hypoxia. Chronic kidney hypoxia is induced by a number of pathogenic conditions, including renal ischemia, reduced peritubular capillary, and tubulointerstitial fibrosis...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28213404/hydrogen-sulfide-alleviates-hypertensive-kidney-dysfunction-through-an-epigenetic-mechanism
#6
Gregory J Weber, Sathnur B Pushpakumar, Utpal Sen
Hypertension is a major risk factor for chronic kidney disease (CKD), and renal inflammation is an integral part in this pathology. Hydrogen sulfide (H2S) has been shown to mitigate renal damage through reduction in blood pressure and ROS; however, the exact mechanisms are not clear. While several studies have underlined the role of epigenetics in renal inflammation and dysfunction, the mechanisms through which epigenetic regulators play a role in hypertension are not well defined. In this study, we sought to identify whether microRNAs are dysregulated in response to angiotensin II (ANG II)-induced hypertension in the kidney and whether a H2S donor, GYY4137, could reverse the microRNA alteration and kidney function...
May 1, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28105334/chronic-kidney-disease-in-children-and-the-role-of-epigenetics-future-therapeutic-trajectories
#7
Samuel N Uwaezuoke, Henrietta U Okafor, Vivian N Muoneke, Odutola I Odetunde, Chioma L Odimegwu
Global differences in the observed causes of chronic kidney disease (CKD) in children are well documented and are attributed to dissimilarities in clime, race, hereditary, and ancestry. Thus, familial clustering and disparities in CKD prevalence rates across ethnic and racial groups indicate that the progression of renal disease has a strong genetic component. Mammalian studies have demonstrated a feasible nexus between nutrition and non-genetic exposure (around the time of conception and in epigenetic changes) in the expression of major genes identified in renal organogenesis...
December 2016: Biomedical Reports
https://www.readbyqxmd.com/read/28097824/mechanisms-of-metabolic-memory-and-renal-hypoxia-as-a-therapeutic-target-in-diabetic-kidney-disease
#8
REVIEW
Yosuke Hirakawa, Tetsuhiro Tanaka, Masaomi Nangaku
Diabetic kidney disease (DKD) is a worldwide public health problem. The definition of DKD is under discussion. Although the term DKD was originally defined as 'kidney disease specific to diabetes,' DKD frequently means chronic kidney disease with diabetes mellitus and includes not only classical diabetic nephropathy, but also kidney dysfunction as a result of nephrosclerosis and other causes. Metabolic memory plays a crucial role in the progression of various complications of diabetes, including DKD. The mechanisms of metabolic memory in DKD are supposed to include advanced glycation end-products, deoxyribonucleic acid methylation, histone modifications and non-coding ribonucleic acid including micro ribonucleic acid...
May 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/27887750/chronic-kidney-disease
#9
REVIEW
Angela C Webster, Evi V Nagler, Rachael L Morton, Philip Masson
The definition and classification of chronic kidney disease (CKD) have evolved over time, but current international guidelines define this condition as decreased kidney function shown by glomerular filtration rate (GFR) of less than 60 mL/min per 1·73 m(2), or markers of kidney damage, or both, of at least 3 months duration, regardless of the underlying cause. Diabetes and hypertension are the main causes of CKD in all high-income and middle-income countries, and also in many low-income countries. Incidence, prevalence, and progression of CKD also vary within countries by ethnicity and social determinants of health, possibly through epigenetic influence...
March 25, 2017: Lancet
https://www.readbyqxmd.com/read/27789733/cigarette-smoking-causes-epigenetic-changes-associated-with-cardiorenal-fibrosis
#10
Christopher A Drummond, Laura E Crotty Alexander, Steven T Haller, Xiaoming Fan, Jeffrey X Xie, David J Kennedy, Jiang Liu, Yanling Yan, Dawn-Alita Hernandez, Denzil P Mathew, Christopher J Cooper, Joseph I Shapiro, Jiang Tian
Clinical studies indicate that smoking combustible cigarettes promotes progression of renal and cardiac injury, leading to functional decline in the setting of chronic kidney disease (CKD). However, basic studies using in vivo small animal models that mimic clinical pathology of CKD are lacking. To address this issue, we evaluated renal and cardiac injury progression and functional changes induced by 4 wk of daily combustible cigarette smoke exposure in the 5/6th partial nephrectomy (PNx) CKD model. Molecular evaluations revealed that cigarette smoke significantly (P < 0...
December 1, 2016: Physiological Genomics
https://www.readbyqxmd.com/read/27766038/indoxyl-sulfate-enhance-the-hypermethylation-of-klotho-and-promote-the-process-of-vascular-calcification-in-chronic-kidney-disease
#11
Jing Chen, Xiaoyan Zhang, Han Zhang, Tongqiang Liu, Hui Zhang, Jie Teng, Jun Ji, Xiaoqiang Ding
Chronic kidney disease (CKD) is a state of Klotho deficiency. The Klotho expression may be suppressed due to DNA hypermethylation in cancer cells so we have investigated the effects and possible mechanisms by which Klotho expression is regulated in human aortic smooth muscle cells (HASMCs). The vascular Klotho hypermethylation in radial arteries of patients with end-stage renal disease was described. Cultured HASMCs and 5/6-nephrectomized Sprague Dawley (SD) rats treated with indoxyl sulfate (IS) were used as in vitro and in vivo models, respectively...
2016: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/27760772/downregulation-of-kidney-protective-factors-by-inflammation-role-of-transcription-factors-and-epigenetic-mechanisms
#12
REVIEW
Olga Ruiz-Andres, Maria Dolores Sanchez-Niño, Juan Antonio Moreno, Marta Ruiz-Ortega, Adrian Mario Ramos, Ana Belen Sanz, Alberto Ortiz
Chronic kidney disease (CKD) is associated to an increased risk of death, CKD progression, and acute kidney injury (AKI) even from early stages, when glomerular filtration rate (GFR) is preserved. The link between early CKD and these risks is unclear, since there is no accumulation of uremic toxins. However, pathological albuminuria and kidney inflammation are frequent features of early CKD, and the production of kidney protective factors may be decreased. Indeed, Klotho expression is already decreased in CKD category G1 (normal GFR)...
December 1, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27760046/the-long-noncoding-rna-tug1-connects-metabolic-changes-with-kidney-disease-in-podocytes
#13
Szu Yuan Li, Katalin Susztak
An increasing amount of evidence suggests that metabolic alterations play a key role in chronic kidney disease (CKD) pathogenesis. In this issue of the JCI, Long et al. report that the long noncoding RNA (lncRNA) taurine-upregulated 1 (Tug1) contributes to CKD development. The authors show that Tug1 regulates mitochondrial function in podocytes by epigenetic targeting of expression of the transcription factor PPARγ coactivator 1α (PGC-1α, encoded by Ppargc1a). Transgenic overexpression of Tug1 specifically in podocytes ameliorated diabetes-induced CKD in mice...
November 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27703201/rhein-reversal-of-dna-hypermethylation-associated-klotho-suppression-ameliorates-renal-fibrosis-in-mice
#14
Qin Zhang, Shasha Yin, Lin Liu, Zhihong Liu, Wangsen Cao
Renal fibrosis is the hallmark of chronic kidney diseases (CKD) and its development and progression are significantly affected by epigenetic modifications. Rhein, a plant-derived anthraquinone, displays strong anti-fibrosis properties, but its protective mode of action remains incompletely understood. Here we explore the mechanism of Rhein anti-renal fibrosis by investigating its regulation of Klotho, a known renal anti-fibrotic protein whose suppression after renal injury reportedly involves aberrant DNA methylation...
October 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27692563/low-dose-hydralazine-prevents-fibrosis-in-a-murine-model-of-acute-kidney-injury-to-chronic-kidney-disease-progression
#15
Björn Tampe, Ulrike Steinle, Désirée Tampe, Julienne L Carstens, Peter Korsten, Elisabeth M Zeisberg, Gerhard A Müller, Raghu Kalluri, Michael Zeisberg
Acute kidney injury (AKI) and progressive chronic kidney disease (CKD) are intrinsically tied syndromes. In this regard, the acutely injured kidney often does not achieve its full regenerative capacity and AKI directly transitions into progressive CKD associated with tubulointerstitial fibrosis. Underlying mechanisms of such AKI-to-CKD progression are still incompletely understood and specific therapeutic interventions are still elusive. Because epigenetic modifications play a role in maintaining tissue fibrosis, we used a murine model of ischemia-reperfusion injury to determine whether aberrant promoter methylation of RASAL1 contributes causally to the switch between physiological regeneration and tubulointerstitial fibrogenesis, a hallmark of AKI-to-CKD progression...
January 2017: Kidney International
https://www.readbyqxmd.com/read/27660122/fatty-liver-and-chronic-kidney-disease-novel-mechanistic-insights-and-therapeutic-opportunities
#16
REVIEW
Giovanni Musso, Maurizio Cassader, Solomon Cohney, Franco De Michieli, Silvia Pinach, Francesca Saba, Roberto Gambino
Chronic kidney disease (CKD) is a risk factor for end-stage renal disease (ESRD) and cardiovascular disease (CVD). ESRD or CVD develop in a substantial proportion of patients with CKD receiving standard-of-care therapy, and mortality in CKD remains unchanged. These data suggest that key pathogenetic mechanisms underlying CKD progression go unaffected by current treatments. Growing evidence suggests that nonalcoholic fatty liver disease (NAFLD) and CKD share common pathogenetic mechanisms and potential therapeutic targets...
October 2016: Diabetes Care
https://www.readbyqxmd.com/read/27617141/genetic-considerations-in-pediatric-chronic-kidney-disease
#17
REVIEW
Lyndsay A Harshman, Diana Zepeda-Orozco
Chronic kidney disease (CKD) in children is an irreversible process that, in some cases, may lead to end-stage renal disease. The majority of children with CKD have a congenital disorder of the kidney or urological tract arising from birth. There is strong evidence for both a genetic and epigenetic component to progression of CKD. Utilization of gene-mapping strategies, ranging from genome-wide association studies to single-nucleotide polymorphism analysis, serves to identify potential genetic variants that may lend to disease variation...
March 2016: Journal of Pediatric Genetics
https://www.readbyqxmd.com/read/27540045/impaired-vascular-function-contributes-to-exercise-intolerance-in-chronic-kidney-disease
#18
Amaryllis H Van Craenenbroeck, Emeline M Van Craenenbroeck, Katrijn Van Ackeren, Vicky Y Hoymans, Gert A Verpooten, Christiaan J Vrints, Marie M Couttenye
BACKGROUND: Exercise intolerance is an important feature in patients with chronic kidney disease (CKD) and is prognostic for both increased morbidity and mortality. Little is known about the underlying mechanisms in predialysis CKD. This study aimed to gain more insight into the role of vascular dysfunction in the exercise intolerance of predialysis CKD. In addition, vascular-related microRNAs (miRNAs)-as epigenetic regulators of exercise capacity-were analysed. METHODS: Sixty-three patients with CKD stages 1-5 and 18 healthy controls were included...
December 2016: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/27521506/new-pharmacologic-agents-that-target-inflammation-and-fibrosis-in-nonalcoholic-steatohepatitis-related-kidney-disease
#19
Giovanni Musso, Franco De Michieli, Daria Bongiovanni, Renato Parente, Luciana Framarin, Nicola Leone, Mara Berrutti, Roberto Gambino, Maurizio Cassader, Solomon Cohney, Elena Paschetta
Epidemiologic data show an association between the prevalence and severity of nonalcoholic fatty liver disease and the incidence and stage of chronic kidney disease (CKD); furthermore, nonalcoholic steatohepatitis (NASH)-related cirrhosis has a higher risk of renal failure, a greater necessity for simultaneous liver-kidney transplantation, and a poorer renal outcome than cirrhosis of other etiologies even after simultaneous liver-kidney transplantation. These data suggest that NASH and CKD share common proinflammatory and profibrotic mechanisms of progression, which are targeted incompletely by current treatments...
August 10, 2016: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/27194714/the-proximal-tubule-is-the-primary-target-of-injury-and-progression-of-kidney-disease-role-of-the-glomerulotubular-junction
#20
REVIEW
Robert L Chevalier
There is an alarming global increase in the incidence of end-stage kidney disease, for which early biomarkers and effective treatment options are lacking. Largely based on the histology of the end-stage kidney and on the model of unilateral ureteral obstruction, current investigation is focused on the pathogenesis of renal interstitial fibrosis as a central mechanism in the progression of chronic kidney disease (CKD). It is now recognized that cumulative episodes of acute kidney injury (AKI) can lead to CKD, and, conversely, CKD is a risk factor for AKI...
July 1, 2016: American Journal of Physiology. Renal Physiology
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