The role of protein arginine methyltransferases in kidney diseases

2020 ◽  
Vol 134 (15) ◽  
pp. 2037-2051
Author(s):  
Chunyun Zhang ◽  
Shougang Zhuang
Keyword(s):  
Kidney Diseases ◽  
Kidney Injury ◽  
Renal Tumors ◽  
Post Translational Modification ◽  
Protein Arginine Methyltransferases ◽  
Extracellular Signaling ◽  
Metabolic Products ◽  
Arginine Residues ◽  
And Oxidative Stress

Abstract The methylation of arginine residues by protein arginine methyltransferases (PRMTs) is a crucial post-translational modification for many biological processes, including DNA repair, RNA processing, and transduction of intra- and extracellular signaling. Previous studies have reported that PRMTs are extensively involved in various pathologic states, including cancer, inflammation, and oxidative stress reaction. However, the role of PRMTs has not been well described in kidney diseases. Recent studies have shown that aberrant function of PRMTs and its metabolic products—symmetric dimethylarginine (SDMA) and asymmetric dimethylarginine (ADMA)—are involved in several renal pathological processes, including renal fibrosis, acute kidney injury (AKI), diabetic nephropathy (DN), hypertension, graft rejection and renal tumors. We aim in this review to elucidate the possible roles of PRMTs in normal renal function and various kidney diseases.

scholarly journals Are STATS Arginine-methylated?

2005 ◽  
Vol 280 (23) ◽  
pp. 21700-21705 ◽  
Author(s):  
Waraporn Komyod ◽  
Uta-Maria Bauer ◽  
Peter C. Heinrich ◽  
Serge Haan ◽  
Iris Behrmann
Keyword(s):  
Arginine Methylation ◽  
Signaling Cascades ◽  
Post Translational Modification ◽  
Protein Arginine Methyltransferases ◽  
Stat Proteins ◽  
Fibrosarcoma Cells ◽  
Catalytically Active ◽  
Interferon Resistance ◽  
Stat Pathway

Transcription factors of the STAT (signal transducer and activator of transcription) family are important in signal transduction of cytokines. They are subject to post-translational modification by phosphorylation on tyrosine and serine residues. Recent evidence suggested that STATs are methylated on a conserved arginine residue within the N-terminal region. STAT arginine methylation has been described to be important for STAT function and loss of arginine methylation was discussed to be involved in interferon resistance of cancer cells. Here we provide several independent lines of evidence indicating that the issue of arginine methylation of STATs has to be reassessed. First, we show that treatment of melanoma and fibrosarcoma cells with inhibitors used to suppress methylation (N-methyl-2-deoxyadenosine, adenosine, dl-homocysteine) had profound and rapid effects on phosphorylation of STAT1 and STAT3 but also on p38 and Erk signaling cascades which are known to cross-talk with the Jak/STAT pathway. Second, we show that anti-methylarginine antibodies did not precipitate specifically STAT1 or STAT3. Third, we show that mutation of Arg31 to Lys led to destabilization of STAT1 and STAT3, implicating an important structural role of Arg31. Finally, purified catalytically active protein arginine methyltransferases (PRMT1, -2, -3, -4, and -6) did not methylate STAT proteins, and cotransfection with PRMT1 did not affect STAT1-controlled reporter gene activity. Taken together, our data suggest the absence of arginine methylation of STAT1 and STAT3.

scholarly journals Characterization of the Drosophila protein arginine methyltransferases DART1 and DART4

2004 ◽  
Vol 379 (2) ◽  
pp. 283-289 ◽  
Author(s):  
Marie-Chloé BOULANGER ◽  
Tina Branscombe MIRANDA ◽  
Steven CLARKE ◽  
Marco di FRUSCIO ◽  
Beat SUTER ◽  
...  
Keyword(s):  
Rna Binding ◽  
Developmental Stages ◽  
Rna Binding Proteins ◽  
Genetic System ◽  
Arginine Methylation ◽  
Type I ◽  
Protein Arginine Methyltransferases ◽  
Arginine Residues ◽  
Drosophila Protein

The role of arginine methylation in Drosophila melanogaster is unknown. We identified a family of nine PRMTs (protein arginine methyltransferases) by sequence homology with mammalian arginine methyltransferases, which we have named DART1 to DART9 (Drosophilaarginine methyltransferases 1–9). In keeping with the mammalian PRMT nomenclature, DART1, DART4, DART5 and DART7 are the putative homologues of PRMT1, PRMT4, PRMT5 and PRMT7. Other DART family members have a closer resemblance to PRMT1, but do not have identifiable homologues. All nine genes are expressed in Drosophila at various developmental stages. DART1 and DART4 have arginine methyltransferase activity towards substrates, including histones and RNA-binding proteins. Amino acid analysis of the methylated arginine residues confirmed that both DART1 and DART4 catalyse the formation of asymmetrical dimethylated arginine residues and they are type I arginine methyltransferases. The presence of PRMTs in D. melanogaster suggest that flies are a suitable genetic system to study arginine methylation.

scholarly journals The Role of PGC-1α and Mitochondrial Biogenesis in Kidney Diseases

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 347 ◽  
Author(s):  
Miguel Fontecha-Barriuso ◽  
Diego Martin-Sanchez ◽  
Julio Manuel Martinez-Moreno ◽  
Maria Monsalve ◽  
Adrian Mario Ramos ◽  
...  
Keyword(s):  
Mitochondrial Biogenesis ◽  
Kidney Diseases ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Pde Inhibitors ◽  
Its Gene ◽  
Attractive Therapeutic Target ◽  
Amp Activated Protein Kinase

Chronic kidney disease (CKD) is one of the fastest growing causes of death worldwide, emphasizing the need to develop novel therapeutic approaches. CKD predisposes to acute kidney injury (AKI) and AKI favors CKD progression. Mitochondrial derangements are common features of both AKI and CKD and mitochondria-targeting therapies are under study as nephroprotective agents. PGC-1α is a master regulator of mitochondrial biogenesis and an attractive therapeutic target. Low PGC-1α levels and decreased transcription of its gene targets have been observed in both preclinical AKI (nephrotoxic, endotoxemia, and ischemia-reperfusion) and in experimental and human CKD, most notably diabetic nephropathy. In mice, PGC-1α deficiency was associated with subclinical CKD and predisposition to AKI while PGC-1α overexpression in tubular cells protected from AKI of diverse causes. Several therapeutic strategies may increase kidney PGC-1α activity and have been successfully tested in animal models. These include AMP-activated protein kinase (AMPK) activators, phosphodiesterase (PDE) inhibitors, and anti-TWEAK antibodies. In conclusion, low PGC-1α activity appears to be a common feature of AKI and CKD and recent characterization of nephroprotective approaches that increase PGC-1α activity may pave the way for nephroprotective strategies potentially effective in both AKI and CKD.

scholarly journals Urotensin-II: More Than a Mediator for Kidney

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Ayşe Balat ◽  
Mithat Büyükçelik
Keyword(s):  
Oxidative Stress ◽  
Transforming Growth Factor ◽  
Kidney Diseases ◽  
Active Role ◽  
Renal Physiology ◽  
Urotensin Ii ◽  
Glomerular Diseases ◽  
Stress Mediators ◽  
And Oxidative Stress

Human urotensin-II (hU-II) is one of the most potent vasoconstrictors in mammals. Although both hU-II and its receptor, GPR14, are detected in several tissues, kidney is a major source of U-II in humans. Recent studies suggest that U-II may have a possible autocrine/paracrine functions in kidney and may be an important target molecule in studying renal pathophysiology. It has several effects on tubular transport and probably has active role in renal hemodynamics. Although it is an important peptide in renal physiology, certain diseases, such as hypertension and glomerulonephritis, may alter the expression of U-II. As might be expected, oxidative stress, mediators, and inflammation are like a devil's triangle in kidney diseases, mostly they induce each other. Since there is a complex relationship between U-II and oxidative stress, and other mediators, such as transforming growth factorβ1 and angiotensin II, U-II is more than a mediator in glomerular diseases. Although it is an ancient peptide, known for 31 years, it looks like that U-II will continue to give new messages as well as raising more questions as research on it increases. In this paper, we mainly discuss the possible role of U-II on renal physiology and its effect on kidney diseases.

Mitochondrial dysfunction and the AKI-to-CKD transition

2020 ◽  
Vol 319 (6) ◽  
pp. F1105-F1116
Author(s):  
Mingzhu Jiang ◽  
Mi Bai ◽  
Juan Lei ◽  
Yifan Xie ◽  
Shuang Xu ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Mitochondrial Homeostasis ◽  
Cycle Arrest ◽  
Persistent Inflammation ◽  
Acute Injuries ◽  
Nephron Loss ◽  
Effective Therapeutic Strategy

Acute kidney injury (AKI) has been widely recognized as an important risk factor for the occurrence and development of chronic kidney disease (CKD). Even milder AKI has adverse consequences and could progress to renal fibrosis, which is the ultimate common pathway for various terminal kidney diseases. Thus, it is urgent to develop a strategy to hinder the transition from AKI to CKD. Some mechanisms of the AKI-to-CKD transition have been revealed, such as nephron loss, cell cycle arrest, persistent inflammation, endothelial injury with vascular rarefaction, and epigenetic changes. Previous studies have elucidated the pivotal role of mitochondria in acute injuries and demonstrated that the fitness of this organelle is a major determinant in both the pathogenesis and recovery of organ function. Recent research has suggested that damage to mitochondrial function in early AKI is a crucial factor leading to tubular injury and persistent renal insufficiency. Dysregulation of mitochondrial homeostasis, alterations in bioenergetics, and organelle stress cross talk contribute to the AKI-to-CKD transition. In this review, we focus on the pathophysiology of mitochondria in renal recovery after AKI and progression to CKD, confirming that targeting mitochondria represents a potentially effective therapeutic strategy for the progression of AKI to CKD.

scholarly journals The Role of Sirtuins in Kidney Diseases

2020 ◽  
Vol 21 (18) ◽  
pp. 6686
Author(s):  
Yu Ah Hong ◽  
Ji Eun Kim ◽  
Minjee Jo ◽  
Gang-Jee Ko
Keyword(s):  
Histone Deacetylases ◽  
Energy Homeostasis ◽  
Molecular Mechanisms ◽  
Kidney Diseases ◽  
Expression Profiles ◽  
Kidney Injury ◽  
Class Iii ◽  
Cellular Functions ◽  
Wide Range

Sirtuins (SIRTs) are class III histone deacetylases (HDACs) that play important roles in aging and a wide range of cellular functions. Sirtuins are crucial to numerous biological processes, including proliferation, DNA repair, mitochondrial energy homeostasis, and antioxidant activity. Mammals have seven different sirtuins, SIRT1–7, and the diverse biological functions of each sirtuin are due to differences in subcellular localization, expression profiles, and cellular substrates. In this review, we summarize research advances into the role of sirtuins in the pathogenesis of various kidney diseases including acute kidney injury, diabetic kidney disease, renal fibrosis, and kidney aging along with the possible underlying molecular mechanisms. The available evidence indicates that sirtuins have great potential as novel therapeutic targets for the prevention and treatment of kidney diseases.

scholarly journals GLP-1 receptor agonist ameliorates obesity-induced chronic kidney injury via restoring renal lipid and energy metabolism homeostasis: revealed by metabolomics

2017 ◽  
Author(s):  
Chengshi Wang ◽  
Ling Li ◽  
Shuyun Liu ◽  
Guangneng Liao ◽  
Younan Chen ◽  
...  
Keyword(s):  
Renal Function ◽  
Energy Metabolism ◽  
High Fat Diet ◽  
Receptor Agonist ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Direct Role ◽  
Chronic Kidney Injury ◽  
Metabolomic Data

AbstractIncreasing evidence indicate that obesity is highly associated with chronic kidney disease (CKD).GLP-1 receptor (GLP-1R) agonist has shown benefits on kidney diseases, but its direct role on kidney metabolism in obesity is still not clear. This study aims to investigate the protection and metabolic modulation role of liraglutide (Lira) on kidney of obesity. Rats were induced obese by high-fat diet (HFD), and renal function and metabolism changes were evaluated by metabolomic, biological and histological methods. HFD rats exhibited metabolic disorders including elevated body weight, hyperlipidemia and impaired glucose tolerance, and remarkable renal injuries including declined renal function and inflammatory/fibrotic changes, whereas Lira significantly ameliorated these adverse effects in HFD rats. Metabolomic data showed that Lira reduced renal lipids including fatty acid residues, cholesterol, phospholipids and triglycerides, and improved mitochondria metabolites such as succinate, citrate, taurine, fumarate and NAD+ in the kidney of HDF rats. Furthermore, we revealed that Lira inhibited renal lipid accumulation by coordinating lipogenic and lipolytic signals, and rescued renal mitochondria function via Sirt1/AMPK/PGC1α pathways in HDF rats. This study suggested that Lira alleviated HFD-induced kidney injury via directly restoring renal lipid and energy metabolism, and GLP-1 receptor agonist is a promising therapy for obesity-associated CKD.

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 IL-20 in Acute Kidney Injury: Role in Pathogenesis and Potential as a Therapeutic Target

2020 ◽  
Vol 21 (3) ◽  
pp. 1009
Author(s):  
Tian-Yu Lin ◽  
Yu-Hsiang Hsu
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Risk Factor ◽  
Renal Fibrosis ◽  
Inflammatory Mediator ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Renal Diseases ◽  
Pro Inflammatory Cytokines

Acute kidney injury (AKI) causes over 1 million deaths worldwide every year. AKI is now recognized as a major risk factor in the development and progression of chronic kidney disease (CKD). Diabetes is the main cause of CKD as well. Renal fibrosis and inflammation are hallmarks in kidney diseases. Various cytokines contribute to the progression of renal diseases; thus, many drugs that specifically block cytokine function are designed for disease amelioration. Numerous studies showed IL-20 functions as a pro-inflammatory mediator to regulate cytokine expression in several inflammation-mediated diseases. In this review, we will outline the effects of pro-inflammatory cytokines in the pathogenesis of AKI and CKD. We also discuss the role of IL-20 in kidney diseases and provide a potential therapeutic approach of IL-20 blockade for treating renal diseases.

scholarly journals Inflammaging and Complement System: A Link Between Acute Kidney Injury and Chronic Graft Damage

2020 ◽  
Vol 11 ◽  
Author(s):  
Rossana Franzin ◽  
Alessandra Stasi ◽  
Marco Fiorentino ◽  
Giovanni Stallone ◽  
Vincenzo Cantaluppi ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Complement System ◽  
Kidney Diseases ◽  
Critical Role ◽  
Graft Function ◽  
Kidney Injury ◽  
Increased Risk ◽  
Wide Range ◽  
Renal Aging

The aberrant activation of complement system in several kidney diseases suggests that this pillar of innate immunity has a critical role in the pathophysiology of renal damage of different etiologies. A growing body of experimental evidence indicates that complement activation contributes to the pathogenesis of acute kidney injury (AKI) such as delayed graft function (DGF) in transplant patients. AKI is characterized by the rapid loss of the kidney’s excretory function and is a complex syndrome currently lacking a specific medical treatment to arrest or attenuate progression in chronic kidney disease (CKD). Recent evidence suggests that independently from the initial trigger (i.e., sepsis or ischemia/reperfusions injury), an episode of AKI is strongly associated with an increased risk of subsequent CKD. The AKI-to-CKD transition may involve a wide range of mechanisms including scar-forming myofibroblasts generated from different sources, microvascular rarefaction, mitochondrial dysfunction, or cell cycle arrest by the involvement of epigenetic, gene, and protein alterations leading to common final signaling pathways [i.e., transforming growth factor beta (TGF-β), p16ink4a, Wnt/β-catenin pathway] involved in renal aging. Research in recent years has revealed that several stressors or complications such as rejection after renal transplantation can lead to accelerated renal aging with detrimental effects with the establishment of chronic proinflammatory cellular phenotypes within the kidney. Despite a greater understanding of these mechanisms, the role of complement system in the context of the AKI-to-CKD transition and renal inflammaging is still poorly explored. The purpose of this review is to summarize recent findings describing the role of complement in AKI-to-CKD transition. We will also address how and when complement inhibitors might be used to prevent AKI and CKD progression, therefore improving graft function.

Sign in / Sign up

Export Citation Format

Share Document