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epigenetics in CKD

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https://www.readbyqxmd.com/read/29197521/high-phosphate-induced-downregulation-of-ppar%C3%AE-contributes-to-ckd-associated-vascular-calcification
#1
Liang Liu, Yong Liu, Ying Zhang, Xianjin Bi, Ling Nie, Chi Liu, Jiachuan Xiong, Ting He, Xinlin Xu, Yanlin Yu, Ke Yang, Jun Gu, Yunjian Huang, Jingbo Zhang, Zhiren Zhang, Bo Zhang, Jinghong Zhao
Medial arterial calcification associated with hyperphosphatemia is a main cause of cardiovascular mortality in patients with chronic kidney disease (CKD), but the mechanisms underlying high phosphate-induced vascular calcification remain largely unknown. Here, we observed a significant decrease in the expression of peroxisome proliferator-activated receptor-gamma (PPARγ) in calcified arteries both in CKD patients and in a mouse model of CKD with hyperphosphatemia. In vitro, high phosphate treatment led to a decreased expression of PPARγ in mouse vascular smooth muscle cells (VMSCs), accompanied by apparent osteogenic differentiation and calcification...
November 29, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29195902/indoxyl-sulfate-accelerates-vascular-smooth-muscle-cell-calcification-via-microrna-29b-dependent-regulation-of-wnt-%C3%AE-catenin-signaling
#2
Han Zhang, Jing Chen, Ziyan Shen, Yulu Gu, Linghan Xu, Jiachang Hu, Xiaoyan Zhang, Xiaoqiang Ding
Vascular calcification (VC) is a very common phenomenon in patients with chronic kidney disease(CKD) and it increases the incidence of cardiovascular disease and leads to high mortality in CKD patients. It has been reported that some microRNAs (miRs) play roles in vascular calcification as an epigenetic regulator. Indoxyl sulfate (IS) is a protein-bound uremic toxin which has been proven as one of the major risk factors of cardiovascular disease in CKD. Here we investigated whether microRNA-29b (miR-29b) is involved in IS-induced vascular calcification...
November 28, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29097680/epigenome-wide-association-studies-identify-dna-methylation-associated-with-kidney-function
#3
Audrey Y Chu, Adrienne Tin, Pascal Schlosser, Yi-An Ko, Chengxiang Qiu, Chen Yao, Roby Joehanes, Morgan E Grams, Liming Liang, Caroline A Gluck, Chunyu Liu, Josef Coresh, Shih-Jen Hwang, Daniel Levy, Eric Boerwinkle, James S Pankow, Qiong Yang, Myriam Fornage, Caroline S Fox, Katalin Susztak, Anna Köttgen
Chronic kidney disease (CKD) is defined by reduced estimated glomerular filtration rate (eGFR). Previous genetic studies have implicated regulatory mechanisms contributing to CKD. Here we present epigenome-wide association studies of eGFR and CKD using whole-blood DNA methylation of 2264 ARIC Study and 2595 Framingham Heart Study participants to identify epigenetic signatures of kidney function. Of 19 CpG sites significantly associated (P < 1e-07) with eGFR/CKD and replicated, five also associate with renal fibrosis in biopsies from CKD patients and show concordant DNA methylation changes in kidney cortex...
November 3, 2017: Nature Communications
https://www.readbyqxmd.com/read/28969091/cellular-senescence-senescence-associated-secretory-phenotype-and-chronic-kidney-disease
#4
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...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28910789/end-stage-renal-disease-inflammation-and-cardiovascular-outcomes
#5
Lu Dai, Edyta Golembiewska, Bengt Lindholm, Peter Stenvinkel
Despite marked improvements in renal replacement therapy during the last 30 years, the age-adjusted mortality rate in end-stage renal disease (ESRD) patients is still unacceptably high and comparable to that of many malignancies. Cardiovascular disease (CVD) remains the major cause of morbidity and mortality in ESRD patients. However, traditional risk factors can only partially explain the high premature cardiovascular burden in this population. Nontraditional risk factors, including persistent low-grade inflammation, are critical in the pathogenesis of atherosclerosis, vascular calcification, and other causes of CVD and may also contribute to protein-energy wasting and other complications in chronic kidney disease (CKD) patients...
2017: Contributions to Nephrology
https://www.readbyqxmd.com/read/28777303/novel-biomarkers-in-the-diagnosis-of-chronic-kidney-disease-and-the-prediction-of-its-outcome
#6
REVIEW
Jacek Rysz, Anna Gluba-Brzózka, Beata Franczyk, Zbigniew Jabłonowski, Aleksandra Ciałkowska-Rysz
In its early stages, symptoms of chronic kidney disease (CKD) are usually not apparent. Significant reduction of the kidney function is the first obvious sign of disease. If diagnosed early (stages 1 to 3), the progression of CKD can be altered and complications reduced. In stages 4 and 5 extensive kidney damage is observed, which usually results in end-stage renal failure. Currently, the diagnosis of CKD is made usually on the levels of blood urea and serum creatinine (sCr), however, sCr has been shown to be lacking high predictive value...
August 4, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28667065/current-epigenetic-aspects-the-clinical-kidney-researcher-should-embrace
#7
REVIEW
Anna Witasp, Amaryllis H Van Craenenbroeck, Paul G Shiels, Tomas J Ekström, Peter Stenvinkel, Louise Nordfors
Chronic kidney disease (CKD), affecting 10-12% of the world's adult population, is associated with a considerably elevated risk of serious comorbidities, in particular, premature vascular disease and death. Although a wide spectrum of causative factors has been identified and/or suggested, there is still a large gap of knowledge regarding the underlying mechanisms and the complexity of the CKD phenotype. Epigenetic factors, which calibrate the genetic code, are emerging as important players in the CKD-associated pathophysiology...
July 15, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28652544/ghrelin-treatment-improves-physical-decline-in-sarcopenia-model-mice-through-muscular-enhancement-and-mitochondrial-activation
#8
Masanori Tamaki, Kazutoshi Miyashita, Aika Hagiwara, Shu Wakino, Hiroyuki Inoue, Kentaro Fujii, Chikako Fujii, Sho Endo, Asuka Uto, Masanori Mitsuishi, Masaaki Sato, Toshio Doi, Hiroshi Itoh
Chronic kidney disease (CKD) impairs physical performance in humans, which leads to a risk of all-cause mortality. In our previous study, we demonstrated that a reduction in muscle mitochondria rather than muscle mass was a major cause of physical decline in 5/6 nephrectomized CKD model mice. Because ghrelin administration has been reported to enhance oxygen utilization in skeletal muscle, we examined the usefulness of ghrelin for a recovery of physical decline in 5/6 nephrectomized C57Bl/6 mice, focusing on the epigenetic modification of peroxisome proliferator activated receptor gamma coactivator-1α (PGC-1α), a master regulator of mitochondrial biogenesis...
2017: Endocrine Journal
https://www.readbyqxmd.com/read/28595179/epigenetic-changes-in-the-acute-kidney-injury-to-chronic-kidney-disease-transition
#9
Masaomi Nangaku, Yosuke Hirakawa, Imari Mimura, Reiko Inagi, Tetsuhiro Tanaka
Previously acute kidney injury (AKI) had been believed to be a transient event, and recovery from AKI had been thought to lead to no consequences. However, recent epidemiological studies have shown that even if there is complete recovery of the kidney function, AKI can eventually result in chronic kidney disease (CKD) and eventually in end-stage kidney disease in the long term. Transition of AKI to CKD is mediated by multiple mechanisms, including aberrant cell cycle arrest and hypoxia. Hypoxia of the kidney is induced by rarefaction of the peritubular capillaries after AKI episodes, and induces inflammation and fibrosis...
June 9, 2017: Nephron
https://www.readbyqxmd.com/read/28566479/targeted-exome-sequencing-identifies-pbx1-as-involved-in-monogenic-congenital-anomalies-of-the-kidney-and-urinary-tract
#10
Laurence Heidet, Vincent Morinière, Charline Henry, Lara De Tomasi, Madeline Louise Reilly, Camille Humbert, Olivier Alibeu, Cécile Fourrage, Christine Bole-Feysot, Patrick Nitschké, Frédéric Tores, Marc Bras, Marc Jeanpierre, Christine Pietrement, Dominique Gaillard, Marie Gonzales, Robert Novo, Elise Schaefer, Joëlle Roume, Jelena Martinovic, Valérie Malan, Rémi Salomon, Sophie Saunier, Corinne Antignac, Cécile Jeanpierre
Congenital anomalies of the kidney and urinary tract (CAKUT) occur in three to six of 1000 live births, represent about 20% of the prenatally detected anomalies, and constitute the main cause of CKD in children. These disorders are phenotypically and genetically heterogeneous. Monogenic causes of CAKUT in humans and mice have been identified. However, despite high-throughput sequencing studies, the cause of the disease remains unknown in most patients, and several studies support more complex inheritance and the role of environmental factors and/or epigenetics in the pathophysiology of CAKUT...
October 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28489601/cellular-senescence-senescence-associated-secretory-phenotype-and-chronic-kidney-disease
#11
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-diseases
#12
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
#13
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
#14
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...
July 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28228736/stress-signal-network-between-hypoxia-and-er-stress-in-chronic-kidney-disease
#15
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
#16
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
#17
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
#18
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
#19
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 m2, 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
#20
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
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