The Emerging Role of Epigenetic Methylation in Kidney Disease

2021 ◽  
Vol 28 ◽  
Author(s):  
Li Wen ◽  
Hong-liu Yang ◽  
Lin Lin ◽  
Liang Ma ◽  
Ping Fu
Keyword(s):  
Dna Methylation ◽  
Kidney Disease ◽  
Histone Methylation ◽  
Kidney Diseases ◽  
Therapeutic Approaches ◽  
Promoter Regions ◽  
Recent Advances ◽  
Epigenetic Methylation

: Kidney disease has complex and multifactorial pathophysiology and pathogenesis. Recent studies have revealed that epigenetic methylation changes, namely DNA methylation, histone methylation and non-histone methylation, are strongly implicated in various forms of kidney diseases. This review provides a perspective on the emerging role of epigenetic methylation in kidney disease, including the effects of DNA methylation in diverse promoter regions, regulation and implication of histone methylation, and recent advances and potential directions related to non-histone methylation. Monitoring or targeting epigenetic methylation has potential to contribute to development of therapeutic approaches for multiple kidney diseases.

DNA methylation and the potential role of demethylating agents in prevention of progressive chronic kidney disease

2018 ◽  
Vol 32 (10) ◽  
pp. 5215-5226 ◽  
Author(s):  
Benjamin P. Larkin ◽  
Sarah J. Glastras ◽  
Hui Chen ◽  
Carol A. Pollock ◽  
Sonia Saad
Keyword(s):  
Chronic Kidney Disease ◽  
Dna Methylation ◽  
Kidney Disease ◽  
Potential Role ◽  
Demethylating Agents

scholarly journals GENETIC KIDNEY DISEASES AS AN UNDERECOGNIZED CAUSE OF CHRONIC KIDNEY DISEASE: THE KEY ROLE OF INTERNATIONAL REGISTRY REPORTS

2021 ◽  
Author(s):  
Roser Torra ◽  
Mónica Furlano ◽  
Alberto Ortiz ◽  
Elisabet Ars
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Kidney Diseases ◽  
Unknown Etiology ◽  
Correct Treatment ◽  
Monogenic Diseases ◽  
High Prevalence ◽  
Incorrect Diagnosis ◽  
Kidney Replacement Therapy

Abstract Inherited kidney diseases (IKDs) are among the leading causes of early-onset chronic kidney disease (CKD) and are responsible for at least 10–15% of cases of kidney replacement therapy (KRT) in adults. Pediatric nephrologists are very aware of the high prevalence of IKDs among their patients, but this is not the case for adult nephrologists. Recent publications have demonstrated that monogenic diseases account for a significant percentage of adult cases of CKD. A substantial number of these patients have received a non-specific/incorrect diagnosis or a diagnosis of CKD of unknown etiology, which precludes correct treatment, follow-up and genetic counseling. There are a number of reasons why genetic kidney diseases are difficult to diagnose in adulthood: a) adult nephrologists, in general, are not knowledgeable about IKDs, b) existence of atypical phenotypes, c) genetic testing is not universally available, d) family history is not always available or may be negative, e) lack of knowledge of various genotype–phenotype relationships, f) conflicting interpretation of the pathogenicity of many sequence variants.

scholarly journals Therapeutic Approaches Targeting Proteostasis in Kidney Disease and Fibrosis

2021 ◽  
Vol 22 (16) ◽  
pp. 8674
Author(s):  
Jia-Huang Chen ◽  
Chia-Hsien Wu ◽  
Chih-Kang Chiang
Keyword(s):  
Kidney Disease ◽  
Er Stress ◽  
Kidney Diseases ◽  
Trigger Factor ◽  
Renal Diseases ◽  
Therapeutic Approaches ◽  
Adaptive Process ◽  
Unfolded Protein ◽  
Molecular Signals ◽  
The Relationship

Pathological insults usually disturb the folding capacity of cellular proteins and lead to the accumulation of misfolded proteins in the endoplasmic reticulum (ER), which leads to so-called “ER stress”. Increasing evidence indicates that ER stress acts as a trigger factor for the development and progression of many kidney diseases. The unfolded protein responses (UPRs), a set of molecular signals that resume proteostasis under ER stress, are thought to restore the adaptive process in chronic kidney disease (CKD) and renal fibrosis. Furthermore, the idea of targeting UPRs for CKD treatment has been well discussed in the past decade. This review summarizes the up-to-date literature regarding studies on the relationship between the UPRs, systemic fibrosis, and renal diseases. We also address the potential therapeutic possibilities of renal diseases based on the modulation of UPRs and ER proteostasis. Finally, we list some of the current UPR modulators and their therapeutic potentials.

The Role of Histone Demethylases in the Transcription Regulation of HOX Genes in PML-RARa+ AML Patients

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 876-876
Author(s):  
Katerina Rejlova ◽  
Karolina Kramarzova ◽  
Meritxell Alberich-Jorda ◽  
Karel Fiser ◽  
Marketa Zaliova ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Histone Methylation ◽  
Hox Genes ◽  
Histone Demethylases ◽  
Atra Treatment ◽  
Hox Gene ◽  
Genes Expression ◽  
Methylation Mark

Abstract Homeobox genes (HOX) encode transcription factors that are frequently deregulated in leukemias. Our previous findings described that HOX gene expression differs among genetically characterized subtypes of pediatric AML with PML-RARa+ patients having the lowest overall HOX gene expression. We observed that HOX gene expression positively correlated with expression of histone 3 lysine 27 (H3K27) demethylases JMJD3 and UTX and negatively with DNA methyltransferase DNMT3b. Interestingly, it has been shown that JMJD3 is a direct target of PML-RARa protein (Martens, JH et al, 2010, Cancer Cell). These findings led us to postulate the hypothesis that reduced levels of HOX genes in PML-RARa+ AML can be caused by the suppressed expression of histone demethylases, such as JMJD3 and UTX, resulting in increased H3K27 methylation and transcription inhibition. We chose PML-RARa+ NB4 cell line to study the role of PML-RARa fusion gene in the regulation of HOX gene expression. To inhibit the effect of PML-RARa we used all-trans retinoic acid (ATRA; 1 uM, 10 uM) which was described to release the block caused by this fusion protein. Expression of particular HOX genes (e.g., HOXA1, HOXA3, HOXA5, HOXA7) together with that of JMJD3 and UTX assessed by qPCR was significantly elevated after ATRA treatment, while gene expression of DNMT3b was decreased. To test whether the reduction in HOX gene expression is directly related to the levels of JMJD3 and UTX, we cultured NB4 cells with a specific inhibitor of these histone demethylases, GSK-J4 (1 uM, 10 uM), in combination with ATRA. This co-treatment led to inhibition of JMJD3 and UTX proteins, followed by significant reduction of HOX genes expression (e.g., HOXA1, HOXA3, HOXA5, HOXA7). This result supports our hypothesis that HOX genes expression is directly related to JMJD3/UTX activity. To determine the effect of ATRA and GSK-J4 on histone marks we have isolated histones by acid extraction and detected the levels of histones by western blot in NB4 ATRA or GSK-J4/ATRA treated cells. We observed that the level of repressive histone methylation mark (trimethylated H3K27; H3K27me3) was decreased after ATRA treatment (activation of JMJD3/UTX) and increased after GSK-J4/ATRA co-treatment (inhibition of JMJD3/UTX). The opposite effect was observed in active histone methylation marks where di- and tri-methylated H3K4 (H3K4me2, H3K4me3) increased after ATRA treatment and decreased after GSK-J4/ATRA co-treatment. H3K9 dimethylated (another repressive histone methylation mark) levels did not change. Next, to investigate the histone code directly in particular HOX genes regions we performed chromatin immunoprecipitation (ChIP) assays. We studied the presence of H3K27me3 and H3K4me2 in 5´UTR genomic region of particular HOX genes (HOXA1, HOXA2, HOXA3, HOXA5, HOXA7) in cells treated with ATRA alone or in the combination with GSK-J4. Preliminary results showed reduction in repressive marks (H3K27me3) upon ATRA treatment, whereas addition of GSK-J4 prevented this decrease. Accordingly, we observed that ATRA/GSK-J4 co-treatment reduced active histone mark H3K4me2. To evaluate the role of DNA methylation in observed expression changes after ATRA treatment we performed bisulfite sequencing of particular promoter sites of HOX genes (e.g., HOXA7, HOXA5). Although we detected decreased DNMT3b gene expression after ATRA treatment there was no change in DNA methylation of CpGs in studied regions. Our results demonstrate that changes in chromatin activity correspond with changes in HOX gene expression. Moreover, ChIP data show direct binding of the modified histones and HOX 5´UTR sites. Our data implicate histone demethylases in regulation of HOX gene expression in PML-RARa+ leukemic blasts. DNA methylation in these particular HOX genes is not involved in the regulation. Elucidating the mechanism of regulation of HOX genes expression can help to understand their role in the leukemogenic process. Supported by GACR P304/12/2214 and GAUK 568213. Disclosures No relevant conflicts of interest to declare.

scholarly journals Use of Lipid-Modifying Agents for the Treatment of Glomerular Diseases

2021 ◽  
Vol 11 (8) ◽  
pp. 820
Author(s):  
Mengyuan Ge ◽  
Sandra Merscher ◽  
Alessia Fornoni
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Recent Progress ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Glomerular Diseases ◽  
Intracellular Lipids ◽  
Lipid Modifying Agents ◽  
Made In

Although dyslipidemia is associated with chronic kidney disease (CKD), it is more common in nephrotic syndrome (NS), and guidelines for the management of hyperlipidemia in NS are largely opinion-based. In addition to the role of circulating lipids, an increasing number of studies suggest that intrarenal lipids contribute to the progression of glomerular diseases, indicating that proteinuric kidney diseases may be a form of “fatty kidney disease” and that reducing intracellular lipids could represent a new therapeutic approach to slow the progression of CKD. In this review, we summarize recent progress made in the utilization of lipid-modifying agents to lower renal parenchymal lipid accumulation and to prevent or reduce kidney injury. The agents mentioned in this review are categorized according to their specific targets, but they may also regulate other lipid-relevant pathways.

scholarly journals The role of metabolic acidosis in chronic kidney diseases

2010 ◽  
Vol 4 (3) ◽  
pp. 367-372
Author(s):  
James C. M. Chan
Keyword(s):  
Chronic Kidney Disease ◽  
Metabolic Acidosis ◽  
Kidney Disease ◽  
Kidney Diseases ◽  
Original Research ◽  
Due Diligence ◽  
Acid Base ◽  
Chronic Kidney Diseases ◽  
Balance Development

Abstract Background and objectives: This review focuses on three areas, basic acid-base physiology especially concerning hydrogen ion balance, development of acidosis in chronic kidney disease (CKD), and the consequences of acidosis. We highlight what is well established, what is less certain, and what is unknown. Method and results: The literature on acidosis in CKD were searched from 2004 to 2010 utilizing PubMed, Google Scholar, and Ovid to augment the classic work on acid base physiology over the past three decades. The original research in endogenous acid production and net acid excretion were reviewed. Touching upon the development of metabolic acidosis in CKD, we focused on the consequences of chronic metabolic acidosis on growth and other important variables. Finally, we recognize the significant issue of patients’ medical non-compliance and presented treatment strategy to counter this problem. Conclusion: The correction of acidosis in chronic kidney disease needs no advocacy. The case is made conclusively. Patient non-compliance because of the medication that needs to be taken several times a day is a problem, requiring due diligence.

scholarly journals Role of SIRT1 in HIV-associated kidney disease

2020 ◽  
Vol 319 (2) ◽  
pp. F335-F344 ◽  
Author(s):  
Xuan Wang ◽  
Ruijie Liu ◽  
Weijia Zhang ◽  
Deborah P. Hyink ◽  
Gokul C. Das ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Drug Targets ◽  
Cell Injury ◽  
Kidney Diseases ◽  
Sirtuin 1 ◽  
Kidney Cells ◽  
Sirt1 Expression ◽  
Hiv 1

Human immunodeficiency virus (HIV) infection of kidney cells can lead to HIV-associated nephropathy (HIVAN) and aggravate the progression of other chronic kidney diseases. Thus, a better understanding of the mechanisms of HIV-induced kidney cell injury is needed for effective therapy against HIV-induced kidney disease progression. We have previously shown that the acetylation and activation of key inflammatory regulators, NF-κB p65 and STAT3, were increased in HIVAN kidneys. Here, we demonstrate the key role of sirtuin 1 (SIRT1) deacetylase in the regulation of NF-κB and STAT3 activity in HIVAN. We found that SIRT1 expression was reduced in the glomeruli of human and mouse HIVAN kidneys and that HIV-1 gene expression was associated with reduced SIRT1 expression and increased acetylation of NF-κB p65 and STAT3 in cultured podocytes. Interestingly, SIRT1 overexpression, in turn, reduced the expression of negative regulatory factor in podocytes stably expressing HIV-1 proviral genes, which was associated with inactivation of NF-κB p65 and a reduction in HIV-1 long terminal repeat promoter activity. In vivo, the administration of the small-molecule SIRT1 agonist BF175 or inducible overexpression of SIRT1 specifically in podocytes markedly attenuated albuminuria, kidney lesions, and expression of inflammatory markers in Tg26 mice. Finally, we showed that the reduction in SIRT1 expression by HIV-1 is in part mediated through miR-34a expression. Together, our data provide a new mechanism of SIRT1 regulation and its downstream effects in HIV-1-infected kidney cells and indicate that SIRT1/miR-34a are potential drug targets to treat HIV-related kidney disease.

scholarly journals The complicated role of mitochondria in the podocyte

2020 ◽  
Vol 319 (6) ◽  
pp. F955-F965
Author(s):  
Nehaben A. Gujarati ◽  
Jessica M. Vasquez ◽  
Daniel F. Bogenhagen ◽  
Sandeep K. Mallipattu
Keyword(s):  
Kidney Disease ◽  
Oxidative Phosphorylation ◽  
Diabetic Kidney Disease ◽  
Kidney Diseases ◽  
Redox Homeostasis ◽  
Experimental Models ◽  
Glomerular Diseases ◽  
Podocyte Injury ◽  
Atp Generation

Mitochondria play a complex role in maintaining cellular function including ATP generation, generation of biosynthetic precursors for macromolecules, maintenance of redox homeostasis, and metabolic waste management. Although the contribution of mitochondrial function in various kidney diseases has been studied, there are still avenues that need to be explored under healthy and diseased conditions. Mitochondrial damage and dysfunction have been implicated in experimental models of podocytopathy as well as in humans with glomerular diseases resulting from podocyte dysfunction. Specifically, in the podocyte, metabolism is largely driven by oxidative phosphorylation or glycolysis depending on the metabolic needs. These metabolic needs may change drastically in the presence of podocyte injury in glomerular diseases such as diabetic kidney disease or focal segmental glomerulosclerosis. Here, we review the role of mitochondria in the podocyte and the factors regulating its function at baseline and in a variety of podocytopathies to identify potential targets for therapy.

COLONIC MICROBIOTA AND CHRONIC KIDNEY DISEASES INTESTINAL MICROBIOTA AND CHRONIC KIDNEY DISEASE. PART II

2019 ◽  
Vol 23 (1) ◽  
pp. 18-31 ◽  
Author(s):  
B. G. Lukichev ◽  
A. Sh. Rumyantsev ◽  
I. Yu. Panina ◽  
V. Akimenko
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Intestinal Microbiota ◽  
Kidney Diseases ◽  
Biologically Active ◽  
Chronic Kidney Diseases ◽  
Mechanical Removal ◽  
Starting Point ◽  
Active Substances

Interest in studying the role of the gastrointestinal tract in maintaining homeostasis in chronic kidney disease is a traditional one. It served, in particular, as a starting point for the creation of enterosorbents. However, if earlier the main attention was paid to the mechanical removal of a number of potentially dangerous biologically active substances, recently an intestinal microbiota has become an object of interest. The first part of the review of the literature on this topic is devoted to questions of terminology, the normal physiology of the colon microbiota. A detailed description of dysbiosis is given. The features of the main groups of microorganisms are reflected. The hypothetical and confirmed interrelations of the intestine-kidney axis are presented. The pathogenetic mechanisms of the influence of colon dysbiosis on the processes of local and systemic inflammation are discussed. The influence of dysbiosis on the state of the kidney parenchyma and its participation in the progression of CKD are debated.

Sign in / Sign up

Export Citation Format

Share Document