scholarly journals Role of Endothelial Glucocorticoid Receptor in the Pathogenesis of Kidney Diseases

2021 ◽  
Vol 22 (24) ◽  
pp. 13295
Author(s):  
Jarosław Przybyciński ◽  
Sylwester Drożdżal ◽  
Leszek Domański ◽  
Violetta Dziedziejko ◽  
Andrzej Pawlik
Keyword(s):  
Kidney Disease ◽  
Glucocorticoid Receptor ◽  
Kidney Diseases ◽  
Cell Metabolism ◽  
Kidney Tissue ◽  
Special Focus ◽  
Inflammatory Processes ◽  
Health And Disease ◽  
Kidney Functions

Glucocorticoids, as multifunctional hormones, are widely used in the treatment of various diseases including nephrological disorders. They are known to affect immunological cells, effectively treating many autoimmune and inflammatory processes. Furthermore, there is a growing body of evidence demonstrating the potent role of glucocorticoids in non-immune cells such as podocytes. Moreover, novel data show additional pathways and processes affected by glucocorticoids, such as the Wnt pathway or autophagy. The endothelium is currently considered as a key organ in the regulation of numerous kidney functions such as glomerular filtration, vascular tone and the regulation of inflammation and coagulation. In this review, we analyse the literature concerning the effects of endothelial glucocorticoid receptor signalling on kidney function in health and disease, with special focus on hypertension, diabetic kidney disease, glomerulopathies and chronic kidney disease. Recent studies demonstrate the potential role of endothelial GR in the prevention of fibrosis of kidney tissue and cell metabolism through Wnt pathways, which could have a protective effect against disease progression. Another important aspect covered in this review is blood pressure regulation though GR and eNOS. We also briefly cover potential therapies that might affect the endothelial glucocorticoid receptor and its possible clinical implications, with special interest in selective or local GR stimulation and potential mitigation of GC treatment side effects.

scholarly journals Pathogenic and protective role of macrophages in kidney disease

2013 ◽  
Vol 305 (1) ◽  
pp. F3-F11 ◽  
Author(s):  
Qi Cao ◽  
Yiping Wang ◽  
David C. H. Harris
Keyword(s):  
Kidney Disease ◽  
Kidney Diseases ◽  
Kidney Tissue ◽  
Human Kidney ◽  
Protective Role ◽  
Therapeutic Use ◽  
Disease Type ◽  
Dual Role ◽  
Murine Models

Macrophages (MΦ) are located throughout kidney tissue, where they play important roles in homeostasis, surveillance, tolerance, and cytoprotection. MΦ are highly heterogeneous cells and exhibit distinct phenotypic and functional characteristics depending on their microenvironment and the disease type and stage. Recent studies have identified a dual role for MΦ in several murine models of kidney disease. In this review, we discuss the pathogenic and protective roles of the various MΦ subsets in experimental and human kidney diseases and summarize current progress toward the therapeutic use of MΦ in kidney diseases.

scholarly journals AUTOSOMAL DOMINANT TUBULOINTERSTITIAL KIDNEY DISEASE

2018 ◽  
Vol 22 (6) ◽  
pp. 9-22 ◽  
Author(s):  
I. G. Kayukov ◽  
V. A. Dobronravov ◽  
O. N. Beresneva ◽  
A. V. Smirnov
Keyword(s):  
Kidney Disease ◽  
Molecular Biology ◽  
Diagnostic Criteria ◽  
Autosomal Dominant ◽  
Kidney Diseases ◽  
Basic Information ◽  
Number Of Genes ◽  
Genes Encoding ◽  
Kidney Functions

In recent years, the definitions and classifications of congenital tubulo-interstitial kidney diseases have been significantly revised. This is primarily due to the achievements in the molecular biology and genetics, which made it possible to significantly clarify the role of a number of genes encoding certain proteins that are closely involved in kidney functions. In 2015, KDIGO proposed to unify the terminology, diagnostic criteria and approaches to monitoring conditions associated with mutations of the MUC1, UMOD, HNF1B and REN genes, which led to the development of ideas about the new nosology - autosomal dominant tubulointerstitial kidney disease (ADTKD). A brief description of the basic information about the ADTKD compiled the content of this message.

scholarly journals Hypertension in Chronic Kidney Disease – Role of Arterial Calcification and Impact on Treatment

2014 ◽  
Vol 9 (2) ◽  
pp. 115 ◽  
Author(s):  
Olivier Phan ◽  
Michel Burnier ◽  
Grégoire Wuerzner ◽  
◽  
◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Kidney Diseases ◽  
Arterial Calcification ◽  
Renal Diseases ◽  
Special Focus ◽  
Key Points ◽  
Two Factors ◽  
Impact On Treatment

Hypertension contributes to the progression of kidney diseases as well as to the occurrence of cardiovascular events such as myocardial infarction, heart failure and stroke. The prevalence of hypertension is elevated in patients with kidney disease, and increases progressively as glomerular filtration rate falls. A better understanding of the mechanisms leading to hypertension in renal diseases has been gained in recent years; in this article we will review the pathogenesis of hypertension in chronic kidney disease (CKD) with a special focus on vascular calcification because calcification is associated with an increased incidence of cardiovascular morbidity in CKD patients. Although calcification of large arteries and blood pressure increase with age, few studies have specifically investigated a possible connection between these two factors as determinants of the severity of hypertension in CKD. Finally, we will review the trends in hypertension treatment in CKD patients. Expanded understanding of the role of CKD as both a cause and a target of hypertension highlights key points of pathophysiology of hypertension and may contribute to the identification of new strategies for its prevention and treatment.

scholarly journals The Role of Cell Metabolism in Innate Immune Memory

2020 ◽  
pp. 1-9
Author(s):  
Anaisa Valido Ferreira ◽  
Jorge Domiguéz-Andrés ◽  
Mihai Gheorghe Netea
Keyword(s):  
Metabolic Pathways ◽  
Tricarboxylic Acid Cycle ◽  
Cell Metabolism ◽  
Innate Immune ◽  
Immune Memory ◽  
Functional Changes ◽  
Trained Immunity ◽  
Health And Disease

Immunological memory is classically attributed to adaptive immune responses, but recent studies have shown that challenged innate immune cells can display long-term functional changes that increase nonspecific responsiveness to subsequent infections. This phenomenon, coined <i>trained immunity</i> or <i>innate immune memory</i>, is based on the epigenetic reprogramming and the rewiring of intracellular metabolic pathways. Here, we review the different metabolic pathways that are modulated in trained immunity. Glycolysis, oxidative phosphorylation, the tricarboxylic acid cycle, amino acid, and lipid metabolism are interplaying pathways that are crucial for the establishment of innate immune memory. Unraveling this metabolic wiring allows for a better understanding of innate immune contribution to health and disease. These insights may open avenues for the development of future therapies that aim to harness or dampen the power of the innate immune response.

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.

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.

FC 062OBESITY AS A CAUSE OF KIDNEY DISEASE - INSIGHTS FROM MENDELIAN RANDOMISATION STUDIES

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Xiaoguang Xu ◽  
James Eales ◽  
Xiao Jiang ◽  
Eleanor Sanderson ◽  
David Scannali ◽  
...  
Keyword(s):  
Waist Circumference ◽  
Kidney Disease ◽  
Renal Disease ◽  
Kidney Diseases ◽  
Causal Effects ◽  
Mendelian Randomisation ◽  
Uk Biobank ◽  
Anthropometric Indices ◽  
Health And Disease ◽  
Kidney Health

Abstract Background and Aims Obesity and kidney diseases are common complex disorders with an increasing clinical and economic impact on healthcare around the globe. We aim to examine if modifiable anthropometric indices of obesity exert putatively causal effects on different measures of kidney health and disease. Method We performed conventional observational and Mendelian randomisation (MR) study to examine if modifiable anthropometric indices of obesity exert putatively causal effects on different kidney health and disease-related phenotypes. These analyses were conducted using approximately 300,000 participants of white-British ancestry from UK Biobank and up to 480,000 participants of predominantly European ancestry from genome-wide association studies. Results The Mendelian randomisation analysis indicated that increasing values of genetically predicted BMI and waist circumference were causally linked to changes in renal function indices including reduced estimated glomerular filtration (PeGFRcystatineC=5.96 × 10-59 for BMI and PeGFRcystatineC=1.72 × 10-69 for waist circumference) and increased blood urea nitrogen (PBUN=2.01 × 10-10 for BMI and PBUN=4.54 × 10-12 for waist circumference) in UK Biobank individuals. These associations were replicated using data from CKDGen Consortium individuals (PeGFRcystatineC=1.47 × 10-5 for BMI and PeGFRcystatineC=7.63 × 10-5 for waist circumference; PBUN=1.96 × 10-4 for BMI and PBUN=3.10 × 10-3 for waist circumference). One standard deviation increase in genetically-predicted BMI and waist circumference decreased the relative odds of kidney health index by 14% and 18% (OR=0.86; 95%CI: 0.82-0.92; P=9.18 × 10-6 for BMI and OR=0.82; 95%CI: 0.75-0.90; P=2.12 × 10-5 for waist circumference). Approximately 13-16% of the causal effect of obesity indices on kidney health was mediated by blood pressure. Obesity increased the risk of both acute and chronic kidney disease of several aetiologies including hypertensive renal disease (OR=1.79; 95%CI: 1.14-2.82; P=1.15 × 10-2 for BMI and OR=2.41; 95%CI: 1.30-4.45; P=5.03 × 10-3 for waist circumference), renal failure (OR=1.51; 95%CI: 1.25-1.83; P=2.60 × 10-5 for BMI and OR=1.86; 95%CI: 1.43-2.42; P=4.16 × 10-6 for waist circumference) and CKD (OR=1.50; 95%CI: 1.16-1.96; P=2.44 × 10-3 for BMI and OR=1.83; 95%CI: 1.28-2.63; P=9.49 × 10-4 for waist circumference) and diabetic nephropathy (OR=1.92; 95%CI: 1.44-2.54; P=6.86 × 10-6 for BMI). Conclusion These findings indicate that obesity is causally linked to indices of renal health and the risk of different kidney diseases. This evidence substantiates the value of weight loss as a strategy of preventing and/or counteracting a decline in kidney health as well as decreasing the risk of renal disease.

scholarly journals TIGAR's promiscuity

2014 ◽  
Vol 458 (3) ◽  
pp. e5-e7 ◽  
Author(s):  
Juan P. Bolaños
Keyword(s):  
Cell Metabolism ◽  
Glucose Consumption ◽  
Pentose Phosphate ◽  
Regulator Protein ◽  
Biochemical Journal ◽  
Cellular Context ◽  
Health And Disease ◽  
Rigorous Study ◽  
Cancer Cell Metabolism

TIGAR [TP53 (tumour protein 53)-induced glycolysis and apoptosis regulator] protein is known for its ability to inhibit glycolysis, shifting glucose consumption towards the pentose phosphate pathway to promote antioxidant protection of cancer cells. According to sequence homology and activity analyses, TIGAR was initially considered to be a fructose-2,6-bisphosphatase; it has thus received much attention in cancer cell metabolism, given its dependence on p53 and the key role of F26BP (fructose 2,6-bisphosphate) at modulating glycolysis and gluconeogenesis. However, in a rigorous study published in this issue of the Biochemical Journal, Gerin and colleagues report that recombinant TIGAR is a 23BPG (2,3-bisphosphoglycerate) phosphatase, although it also dephosphorylates other carboxylic acid-phosphate esters and, weakly, F26BP. As such, inhibition of endogenous TIGAR leads to a dramatic increase in cellular 23BPG, influencing F26BP to a lower extent that depends on the cellular context. These results challenge the currently held notion that TIGAR modulates glycolysis through decreasing F26BP, and opens a yet unrecognized function(s) for TIGAR-mediated 23BPG control of cellular metabolism in health and disease.

Sign in / Sign up

Export Citation Format

Share Document