keyword
https://read.qxmd.com/read/38529500/sexually-dimorphic-renal-expression-of-klotho-is-directed-by-a-kidney-specific-distal-enhancer-responsive-to-hnf1b
#1
Jakub Jankowski, Hye Kyung Lee, Chengyu Liu, Julia Wilflingseder, Lothar Hennighausen
Transcription enhancers are genomic sequences regulating common and tissue-specific genes and their disruption can contribute to human disease development and progression. Klotho , a sexually dimorphic gene specifically expressed in kidney, is well-linked to kidney dysfunction and its deletion from the mouse genome leads to premature aging and death. However, the sexually dimorphic regulation of Klotho is not understood. Here, we characterize two candidate Klotho enhancers using H3K27ac epigenetic marks and transcription factor binding and investigate their functions, individually and combined, through CRISPR-Cas9 genome engineering...
March 4, 2024: bioRxiv
https://read.qxmd.com/read/38521405/hypermethylation-leads-to-the-loss-of-hoxa5-resulting-in-jag1-expression-and-notch-signaling-contributing-to-kidney-fibrosis
#2
JOURNAL ARTICLE
Xiao Xiao, Wei Wang, Chunyuan Guo, Jiazhu Wu, Sheng Zhang, Huidong Shi, Sangho Kwon, Jiankang Chen, Zheng Dong
Epigenetic regulations, including DNA methylation, are critical to the development and progression of kidney fibrosis, but the underlying mechanisms remain elusive. Here, we show that fibrosis of the mouse kidney was associated with the induction of DNA methyltransferases and increases in global DNA methylation and was alleviated by the DNA methyltransferase inhibitor 5-Aza-2'-deoxycytidine (5-Aza). Genome wide analysis demonstrated the hypermethylation of 94 genes in mouse unilateral ureteral obstruction kidneys, which was markedly reduced by 5-Aza...
March 21, 2024: Kidney International
https://read.qxmd.com/read/38516524/growing-concerns-about-using-hypoxia-inducible-factor-prolyl-hydroxylase-inhibitors-for-the-treatment-of-renal-anemia
#3
REVIEW
Takeshi Nakanishi, Takahiro Kuragano
Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) have emerged as a novel therapeutic class for treating anemia in patients with chronic kidney disease. Small molecule analogs of α-ketoglutarate (AKG), an essential substrate for 2-oxoglutarate-dependent dioxygenases (2-OGDDs), including prolyl hydroxylase domain proteins (PHDs), inhibit PHDs pharmacologically and thereby prevent HIF degradation. HIF stabilization alleviates anemia through several stimulatory effects on erythropoiesis, but it also affects the expression of many anemia-unrelated genes whose protein products exert important functions in vivo ...
March 2024: Clinical Kidney Journal
https://read.qxmd.com/read/38474331/comparative-analysis-of-acute-kidney-injury-models-and-related-fibrogenic-responses-convergence-on-methylation-patterns-regulated-by-cold-shock-protein
#4
JOURNAL ARTICLE
Sabine Brandt, Anja Bernhardt, Saskia Häberer, Katharina Wolters, Fabian Gehringer, Charlotte Reichardt, Anna Krause, Robert Geffers, Sascha Kahlfuß, Andreas Jeron, Dunja Bruder, Jonathan A Lindquist, Berend Isermann, Peter R Mertens
BACKGROUND: Fibrosis is characterized by excessive extracellular matrix formation in solid organs, disrupting tissue architecture and function. The Y-box binding protein-1 (YB-1) regulates fibrosis-related genes (e.g., Col1a1 , Mmp2 , and Tgfβ1 ) and contributes significantly to disease progression. This study aims to identify fibrogenic signatures and the underlying signaling pathways modulated by YB-1. METHODS: Transcriptomic changes associated with matrix gene patterns in human chronic kidney diseases and murine acute injury models were analyzed with a focus on known YB-1 targets...
February 20, 2024: Cells
https://read.qxmd.com/read/38424404/the-pharmaco-epigenetics-of-hypertension-a-focus-on-microrna
#5
REVIEW
Serge Yaacoub, Ammar Boudaka, Ali AlKhatib, Gianfranco Pintus, Amirhossein Sahebkar, Firas Kobeissy, Ali H Eid
Hypertension is a major harbinger of cardiovascular morbidity and mortality. It predisposes to higher rates of myocardial infarction, chronic kidney failure, stroke, and heart failure than most other risk factors. By 2025, the prevalence of hypertension is projected to reach 1.5 billion people. The pathophysiology of this disease is multifaceted, as it involves nitric oxide and endothelin dysregulation, reactive oxygen species, vascular smooth muscle proliferation, and vessel wall calcification, among others...
February 29, 2024: Molecular and Cellular Biochemistry
https://read.qxmd.com/read/38387702/significance-of-lncrnas-in-aki-to-ckd-transition-a-therapeutic-and-diagnostic-viewpoint
#6
REVIEW
Bhupendra Puri, Syamantak Majumder, Anil Bhanudas Gaikwad
Acute kidney injury to chronic kidney disease (AKI-to-CKD) transition is a complex intermingling of characteristics of both AKI and CKD. Pathophysiologically, the transition lasts seven days after the AKI episode and thereafter silently progresses towards CKD. Growing reports confirm that the AKI-to-CKD transition is heavily regulated by epigenetic modifiers. Long non-coding RNAs (lncRNAs) share a diverse role in gene regulation at transcriptional and translational levels and have been reported to be involved in the regulation and progression of AKI-to-CKD transition...
February 20, 2024: Life Sciences
https://read.qxmd.com/read/38360205/protein-rich-foods-sea-foods-and-gut-microbiota-amplify-immune-responses-in-chronic-diseases-and-cancers-targeting-perk-as-a-novel-therapeutic-strategy-for-chronic-inflammatory-diseases-neurodegenerative-disorders-and-cancer
#7
REVIEW
Fatma Saaoud, Yifan Lu, Keman Xu, Ying Shao, Domenico Praticò, Roberto I Vazquez-Padron, Hong Wang, Xiaofeng Yang
The endoplasmic reticulum (ER) is a cellular organelle that is physiologically responsible for protein folding, calcium homeostasis, and lipid biosynthesis. Pathological stimuli such as oxidative stress, ischemia, disruptions in calcium homeostasis, and increased production of normal and/or folding-defective proteins all contribute to the accumulation of misfolded proteins in the ER, causing ER stress. The adaptive response to ER stress is the activation of unfolded protein response (UPR), which affect a wide variety of cellular functions to maintain ER homeostasis or lead to apoptosis...
February 13, 2024: Pharmacology & Therapeutics
https://read.qxmd.com/read/38347603/kidney-specific-methylation-patterns-correlate-with-kidney-function-and-are-lost-upon-kidney-disease-progression
#8
JOURNAL ARTICLE
Naor Sagy, Noa Meyrom, Pazit Beckerman, Oren Pleniceanu, Daniel Z Bar
BACKGROUND: 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 the chronological age and predict multiple health-related outcomes. However, why some sites correlating with lifespan, healthspan, or specific medical conditions remain poorly understood. Kidney fibrosis is the common pathway for chronic kidney disease, which affects 10% of European and US populations...
February 12, 2024: Clinical Epigenetics
https://read.qxmd.com/read/38345449/effect-of-indoxyl-sulfate-on-the-morphology-and-function-of-the-thyroid-gland-ex-vivo-studies-in-rabbits
#9
JOURNAL ARTICLE
M Chmurska, A Galuszka, P Pawlicki, M Zarzycka, A Sechman, A Grzegorzewska, P Niedbala, M Kotula-Balak
Indoxyl sulfates are uremic indolic toxins known to participate in the pathogenesis of cardiovascular diseases during chronic kidney disease in humans and some animal species. However, nothing is known about the indoxyl sulfate effect on the thyroid gland which is especially responsible for the general organism metabolism. This study determines the morpho-functional status of the thyroid gland after exposure to indoxyl sulfate (10, 25, and 50 mM) with the use of an ex vivo system and rabbit (n=10) as an experimental model thyroid gland histology, immunoexpression of thyrotropin receptor (TSHR), and concentrations of thyroxine (T4) and triiodothyronine (T3) were evaluated...
December 2023: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://read.qxmd.com/read/38328130/epigenetic-reprogramming-driving-successful-and-failed-repair-in-acute-kidney-injury
#10
Yoshiharu Muto, Eryn E Dixon, Yasuhiro Yoshimura, Nicolas Ledru, Yuhei Kirita, Haojia Wu, Benjamin D Humphreys
Acute kidney injury (AKI) causes epithelial damage followed by subsequent repair. While successful repair restores kidney function, this process is often incomplete and can lead to chronic kidney disease (CKD) in a process called failed repair. To better understand the epigenetic reprogramming driving this AKI-to-CKD transition we generated a single nucleus multiomic atlas for the full mouse AKI time course, consisting of ∼280,000 single nucleus transcriptomes and epigenomes. We reveal cell-specific dynamic alterations in gene regulatory landscapes reflecting especially activation of proinflammatory pathways...
January 23, 2024: bioRxiv
https://read.qxmd.com/read/38322624/trna-derived-small-rnas-a-novel-regulatory-small-noncoding-rna-in-renal-diseases
#11
JOURNAL ARTICLE
Dan Li, Xian Xie, Ni Yin, Xueqin Wu, Bin Yi, Hao Zhang, Wei Zhang
BACKGROUND: tRNA-derived small RNAs (tsRNAs) are an emerging class of small noncoding RNAs derived from tRNA cleavage. SUMMARY: With the development of high-throughput sequencing, various biological roles of tsRNAs have been gradually revealed, including regulation of mRNA stability, transcription, translation, direct interaction with proteins and as epigenetic factors, etc. Recent studies have shown that tsRNAs are also closely related to renal disease. In clinical acute kidney injury (AKI) patients and preclinical AKI models, the production and differential expression of tsRNAs in renal tissue and plasma were observed...
February 2024: Kidney Diseases
https://read.qxmd.com/read/38316761/cellular-senescence-of-renal-tubular-epithelial-cells-in-acute-kidney-injury
#12
REVIEW
Juan Chen, Huhai Zhang, Xiangling Yi, Qian Dou, Xin Yang, Yani He, Jia Chen, Kehong Chen
Cellular senescence represents an irreversible state of cell-cycle arrest during which cells secrete senescence-associated secretory phenotypes, including inflammatory factors and chemokines. Additionally, these cells exhibit an apoptotic resistance phenotype. Cellular senescence serves a pivotal role not only in embryonic development, tissue regeneration, and tumor suppression but also in the pathogenesis of age-related degenerative diseases, malignancies, metabolic diseases, and kidney diseases. The senescence of renal tubular epithelial cells (RTEC) constitutes a critical cellular event in the progression of acute kidney injury (AKI)...
February 5, 2024: Cell Death Discovery
https://read.qxmd.com/read/38287030/unraveling-the-epigenetic-code-human-kidney-dna-methylation-and-chromatin-dynamics-in-renal-disease-development
#13
JOURNAL ARTICLE
Yu Yan, Hongbo Liu, Amin Abedini, Xin Sheng, Matthew Palmer, Hongzhe Li, Katalin Susztak
Epigenetic changes may fill a critical gap in our understanding of kidney disease development, as they not only reflect metabolic changes but are also preserved and transmitted during cell division. We conducted a genome-wide cytosine methylation analysis of 399 human kidney samples, along with single-nuclear open chromatin analysis on over 60,000 cells from 14 subjects, including controls, and diabetes and hypertension attributed chronic kidney disease (CKD) patients. We identified and validated differentially methylated positions associated with disease states, and discovered that nearly 30% of these alterations were influenced by underlying genetic variations, including variants known to be associated with kidney disease in genome-wide association studies...
January 29, 2024: Nature Communications
https://read.qxmd.com/read/38270638/single%C3%A2-cell-multi-omics-of-fibrotic-kidney-reveal-epigenetic-regulation-of-antioxidation-and-apoptosis-within-proximal-tubule
#14
JOURNAL ARTICLE
Zhejun Chen, Liqing Ye, Minyan Zhu, Cong Xia, Junfen Fan, Hongbo Chen, Zhijian Li, Shan Mou
BACKGROUND: Until now, there has been no particularly effective treatment for chronic kidney disease (CKD). Fibrosis is a common pathological change that exist in CKD. METHODS: To better understand the transcriptional dynamics in fibrotic kidney, we make use of single-nucleus assay for transposase-accessible chromatin sequencing (snATAC-seq) and single-cell RNA sequencing (scRNA-seq) from GEO datasets and perform scRNA-seq of human biopsy to seek possible transcription factors (TFs) regulating target genes in the progress of kidney fibrosis across mouse and human kidneys...
January 25, 2024: Cellular and Molecular Life Sciences: CMLS
https://read.qxmd.com/read/38262578/chronic-kidney-disease-and-left-ventricular-diastolic-dysfunction-ckd-lvdd-alter-cardiac-expression-of-mitochondria-related-genes-in-swine
#15
JOURNAL ARTICLE
Alejandro R Chade, Rhys Sitz, Taylor J Kelty, Elizabeth McCarthy, Darla L Tharp, R Scott Rector, Alfonso Eirin
Cardiovascular disease and heart failure doubles in patients with chronic kidney disease (CKD), but the underlying mechanisms remain obscure. Mitochondria are central to maintaining cellular respiration and modulating cardiomyocyte function. We took advantage of our novel swine model of CKD and left ventricular diastolic dysfunction (CKD-LVDD) to investigate the expression of mitochondria-related genes and potential mechanisms regulating their expression. CKD-LVDD and normal control pigs (n=6/group, 3 males/3 females) were studied for 14 weeks...
January 21, 2024: Translational Research: the Journal of Laboratory and Clinical Medicine
https://read.qxmd.com/read/38255221/micrornas-as-potential-graft-rejection-or-tolerance-biomarkers-and-their-dilemma-in-clinical-routines-behaving-like-devilish-angelic-or-frightening-elements
#16
REVIEW
Isabel Legaz, Víctor Jimenez-Coll, Rosana González-López, Marina Fernández-González, María José Alegría-Marcos, José Antonio Galián, Carmen Botella, Rosa Moya-Quiles, Manuel Muro-Pérez, Alfredo Minguela, Santiago Llorente, Manuel Muro
Allograft rejection is a widespread complication in allograft recipients with chronic kidney disease. Undertreatment of subclinical and clinical rejection and later post-transplant problems are caused by an imperfect understanding of the mechanisms at play and a lack of adequate diagnostic tools. Many different biomarkers have been analyzed and proposed to detect and monitor these crucial events in transplant outcomes. In this sense, microRNAs may help diagnose rejection or tolerance and indicate appropriate treatment, especially in patients with chronic allograft rejection...
January 5, 2024: Biomedicines
https://read.qxmd.com/read/38254967/liquid-biopsy-a-new-avenue-for-the-diagnosis-of-kidney-disease-diabetic-kidney-disease-renal-cancer-and-iga-nephropathy
#17
REVIEW
Jill Dybiec, Weronika Frąk, Joanna Kućmierz, Julita Tokarek, Armanda Wojtasińska, Ewelina Młynarska, Jacek Rysz, Beata Franczyk
Kidney diseases are some of the most common healthcare problems. As the population of elderly individuals with concurrent health conditions continues to rise, there will be a heightened occurrence of these diseases. Due to the renal condition being one of the longevity predictors, early diagnosis of kidney dysfunction plays a crucial role. Currently, prevalent diagnostic tools include laboratory tests and kidney tissue biopsies. New technologies, particularly liquid biopsy and new detection biomarkers, hold promise for diagnosing kidney disorders...
January 7, 2024: Genes
https://read.qxmd.com/read/38236471/points-of-view-in-nephrology-personalized-management-of-iga-nephropathy-beyond-kdigo
#18
JOURNAL ARTICLE
Hernán Trimarchi, Fernando C Fervenza, Rosanna Coppo
IgA nephropathy is the most common primary glomerulonephritis worldwide, and an important cause of kidney failure, as 20-40% of patients progress to renal replacement therapy 20-30 years after diagnosis. Its clinical presentation ranges from isolated microscopic hematuria to nephrotic syndrome, and even to a rapidly progressive course. Ethnicity and epigenetics play a key role in its clinical aggressiveness. Selection of patients at risk needing immunosuppressive treatment is a challenge for the nephrologist...
January 18, 2024: Journal of Nephrology
https://read.qxmd.com/read/38146662/epigallocatechin-3-gallate-attenuates-arsenic-induced-fibrogenic-changes-in-human-kidney-epithelial-cells-through-reversal-of-epigenetic-aberrations-and-antioxidant-activities
#19
JOURNAL ARTICLE
Mary Sonia Iheanacho, Ramji Kandel, Priti Roy, Kamaleshwar P Singh
Renal fibrosis is a pathogenic intermediate stage of chronic kidney disease (CKD). Nephrotoxicants including arsenic can cause kidney fibrosis through induction of oxidative stress and epigenetic aberrations. Epigallocatechin-3-gallate (EGCG), a green tea polyphenol, is known to have antioxidant and epigenetic modulation properties. Whether EGCG, through its antioxidant and epigenetic modulating activities, can attenuate fibrogenesis is not known. Therefore, the objective of this study was to determine whether EGCG can attenuate arsenic-induced acute injury and long-term exposure associated fibrogenicity in kidney epithelial cells...
December 26, 2023: BioFactors
https://read.qxmd.com/read/38137521/the-safety-and-efficacy-of-combining-saxagliptin-and-pioglitazone-therapy-in-streptozocin-induced-diabetic-rats
#20
JOURNAL ARTICLE
Ahmed Mohamed Othman, Ibrahim Ashour Ibrahim, Samy M Saleh, Dina M Abo-Elmatty, Noha M Mesbah, Asmaa R Abdel-Hamed
BACKGROUND: Type 2 diabetes mellitus (T2DM) is a chronic progressive disease due to insulin resistance. Oxidative stress complicates the etiology of T2DM. Saxagliptin is a selective dipeptidyl peptidase-4 (DPP-4) inhibitor, while Pioglitazone is a thiazolidinedione insulin sensitizer. This study aimed to assess the effect of Saxagliptin and Pioglitazone monotherapy and combination therapy on the biochemical and biological parameters in streptozotocin (STZ)-induced diabetic rats. METHODS: The study included thirty-five male albino rats...
December 13, 2023: Biomedicines
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