ISN Forefronts Symposium 2015: The Diverse Function of Macrophages in Renal Disease
Ontology highlight
ABSTRACT:
SUBMITTER: Duthie F
PROVIDER: S-EPMC5720538 | biostudies-literature | 2016 Aug
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Diabetic nephropathy (DN) is the major reason for end stage renal disease in the western world. Patients with DN developed more severe cardiovascular complications with worse prognosis. In spite of tight blood pressure and glucose control through applying angiotensin II receptor antagonism, angiotensin receptor inhibitors and even direct renin inhibitors, the progression and development of DN has continued to accelerate. Nuclear receptors are, with few exceptions, ligand-depended transcription factors some of which modulate genes involved in the transportation and metabolism of carbohydrate or lipid, and inflammation. Considering the diverse biological functions of nuclear receptors, efforts have been made to explore their contributions to the pathogenesis of DN and potential therapeutic strategies. This review is mainly focused on the association between various nuclear receptors and the pathogenesis of DN, the potential beneficial effects of targeting these receptors for preventing the progress of DN, and the important role that nuclear receptors may play in future therapeutic strategies for DN.
| S-EPMC5601313 | biostudies-literature
Project description:Hypertension is known as the "silent killer," driving the global public health burden of cardiovascular and renal disease. Blood pressure homeostasis is intimately associated with sodium balance and the distribution of sodium between fluid compartments and within tissues. On a population level, most societies consume 10 times more salt that the 0.5 g required by physiological need. This high salt intake is strongly linked to hypertension and to the World Health Organization targeting a ∼30% relative reduction in mean population salt intake to arrest the global mortality due to cardiovascular disease. But how does a habitually high-salt diet cause blood pressure to rise? In this focused review, we discuss 2 "evolutionary medicine" concepts, presented at the ISN Forefront Meeting "Immunomodulation of Cardio-renal Function." We first examine how ancestral variants in genes that conferred a selection advantage during early human development are now maladaptive. We then discuss the conservation of "renal" sodium transport processes across multiple organ systems, including the brain. These systems influence sodium appetite and can exert an often-overlooked effect on long-term blood pressure control.
| S-EPMC5044930 | biostudies-literature
Project description:This is a summary of the activities and scientific content of the first International Society for Computational Biology Student Council symposium in Africa. This meeting organized by the students for the students took place 8th of March 2015 in Dar Es Salaam, Tanzania.
| S-EPMC4786895 | biostudies-other
Project description:BackgroundMutations affecting cilia proteins have an established role in renal cyst formation. In mice, the rate of cystogenesis is influenced by the age at which cilia dysfunction occurs and whether the kidney has been injured. Disruption of cilia function before postnatal day 12-14 results in rapid cyst formation; however, cyst formation is slower when cilia dysfunction is induced after postnatal day 14. Rapid cyst formation can also be induced in conditional adult cilia mutant mice by introducing renal injury. Previous studies indicate that macrophages are involved in cyst formation, however the specific role and type of macrophages responsible has not been clarified.MethodsWe analyzed resident macrophage number and subtypes during postnatal renal maturation and after renal injury in control and conditional Ift88 cilia mutant mice. We also used a pharmacological inhibitor of resident macrophage proliferation and accumulation to determine the importance of these cells during rapid cyst formation.ResultsOur data show that renal resident macrophages undergo a phenotypic switch from R2b (CD11clo) to R2a (CD11chi) during postnatal renal maturation. The timing of this switch correlates with the period in which cyst formation transitions from rapid to slow following induction of cilia dysfunction. Renal injury induces the reaccumulation of juvenile-like R2b resident macrophages in cilia mutant mice and restores rapid cystogenesis. Loss of primary cilia in injured conditional Ift88 mice results in enhanced epithelial production of membrane-bound CSF1, a cytokine that promotes resident macrophage proliferation. Inhibiting CSF1/CSF1-receptor signaling with a CSF1R kinase inhibitor reduces resident macrophage proliferation, R2b resident macrophage accumulation, and renal cyst formation in two mouse models of cystic disease.ConclusionsThese data uncover an important pathogenic role for resident macrophages during rapid cyst progression.
| S-EPMC6779366 | biostudies-literature
Project description:International Society of Nephrology (ISN) Frontiers meetings build on the success of the ISN Nexus and Forefronts series by bringing together basic scientists, clinicians, and practitioners in a unique setting. This new event was organized to make more innovative science available to a global audience by removing regional barriers in accessing the latest knowledge. The first ISN Frontiers meeting was organized in partnership between the Japanese Society of Nephrology and the Japanese Society for Dialysis Therapy, which was held in Tokyo in February 2018. The meeting focused on the topic “Kidney Disease & Cardiovascular Disease,” which covered a broad range of scientific and clinical fields, including nephrology, cardiovascular diseases, dialysis, transplantation, chronic kidney disease (CKD)–mineral bone disease (MBD), diabetes, pediatric nephrology, nutrition, pharmacology, and nursing. A total of 1584 active physicians and scientists from 64 countries attended the meeting, and a number of leading physician scientists from different and related disciplines of clinical and basic research described and reviewed recent discoveries. This report summarizes the main highlights of the meeting lectures.
| S-EPMC6035142 | biostudies-literature
Project description:BackgroundRecent studies have suggested that macrophages are significantly involved in different renal diseases. However, the role of these renal infiltrating macrophages has not been entirely uncovered. To further clarify the underlying mechanism and identify therapeutic targets, a bioinformatic analysis based on transcriptome profiles was performed.MethodsThree transcription profiling datasets, GSE27045, GSE51466 and GSE75808, were obtained from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were assessed by Gene Ontology (GO) functional annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and gene set enrichment analysis (GSEA).ResultsThe classic signaling pathways and metabolic pathways of macrophages infiltrating the kidney in different pathophysiological processes, including lupus nephritis (LN), renal crystal formation and renal ischemia-reperfusion injury (IRI), were analysed. Furthermore, the common classical pathways significantly altered in the three renal disorders were the oxidative phosphorylation, VEGF signaling and JAK/STAT signaling pathways, while the renin-angiotensin system was uniquely altered in LN, the glycolysis and gluconeogenesis pathways were uniquely altered in models of renal crystal formation, and the calcium signaling pathway was specific to renal IRI.ConclusionsVia bioinformatics analysis, this study revealed the transcriptional features of macrophages in murine LN, renal crystal formation and IRI models, which may serve as promising targets for mechanistic research and the clinical treatment of multiple renal diseases.
| S-EPMC8749068 | biostudies-literature
Project description:BackgroundLow birthweight (LBW) is a worldwide public health problem, demonstrating an increasing incidence in developed countries, including Japan. LBW is also a risk factor for later development of chronic kidney disease (CKD). To date, studies have not evaluated the population impacts of increasing LBW rates on renal function.MethodsEstimated glomerular filtration rate (eGFR) was evaluated in 3737 Japanese adolescent males (15-16 years old) using annual cross-sectional data over an 18-year period (1998-2015).ResultsBetween the initial (1998-2003) and final (2010-15) periods of the study, the mean birthweight decreased from 3213.4?±?383.8 to 3116.2?±?382.3?g and the LBW rate increased from 2.5 to 5.5% (both P???0.01). Additionally, the mean eGFR decreased from 105.1?±?15.9 to 97.4?±?13.8?mL/min/1.73 m2 and the prevalence of mildly reduced renal function (eGFR ??60-?<90 mL/min/1.73 m2) increased from 16.4 to 30.0% (both P???0.01), most evident in the LBW group (from 10.3 to 41.7%, P??0.01). The prevalence of proteinuria also increased significantly. Mildly reduced renal function was significantly associated with LBW [odds ratio (LBW 3000-3999?g) 1.51; 95% confidence interval 1.00-2.55; P?=?0.047].ConclusionsIn this population of Japanese adolescents, the frequency of mildly reduced renal function increased as the LBW frequency increased. Our findings may have implications for the broader Japanese population as well as for other populations in which the prevalence of LBW is increasing.
| S-EPMC5837670 | biostudies-literature
Project description:We show that resident macrophages accumulate in cilia mutant mice prior to cyst formation and that inhibition of resident macrophage accumulation reduces cystic kidney disease.
2019-07-04 | GSE131896 | GEO
Project description:To date, the treatment of immune-mediated kidney diseases has only marginally benefited from highly specific biological drugs that have demonstrated remarkable effects in many other diseases. What accounts for this disparity? In April 2016, the International Society of Nephrology held a Nexus meeting on Translational Immunology in Nephrology in Berlin, Germany, to identify and discuss hurdles that block the translational flow of target identification, and preclinical and clinical target validation in the domain of immune-mediated kidney disease. A broad panel of experts including basic scientists, translational researchers, clinical trialists, pharmaceutical industry drug developers, and representatives of the American and European regulatory authorities made recommendations on how to overcome such hurdles at all levels of the translational research process. The results of these discussions are presented here, which may serve as a roadmap for how to optimize the process of developing more innovative and effective drugs for patients with immune-mediated kidney diseases.
| S-EPMC5720527 | biostudies-literature
Project description:Acute kidney injury has a high mortality and lacks specific therapies, with ischemia/reperfusion injury (IRI) being the predominant cause. Macrophages (M phi) have been used successfully in cell therapy to deliver targeted therapeutic genes in models of inflammatory kidney disease. Heme oxygenase-1 (HO-1) catalyzes heme breakdown and has important cytoprotective functions. We hypothesized that administration of M phi modified to overexpress HO-1 would protect from renal IRI. Using an adenoviral construct (Ad-HO-1), HO-1 was overexpressed in primary bone marrow-derived M phi (BMDM). In vitro Ad-HO-1 M phi showed an anti-inflammatory phenotype with increased phagocytosis of apoptotic cells (ACs) and increased interleukin (IL)-10 but reduced TNF-alpha and nitric oxide (NO) following lipopolysaccharide/interferon-gamma (IFN gamma) stimulation compared to control transduced or unmodified M phi. In vivo, intravenously (IV) injected M phi homed preferentially to the post-IRI kidney compared to uninjured control following experimental IRI. At 24 hours postinjury, despite equivalent levels of tubular necrosis, apoptosis, and capillary density between groups, the injection of Ad-HO-1 M phi resulted in preserved renal function (serum creatinine reduced by 46%), and reduced microvascular platelet deposition. These data demonstrate that genetically modified M phi improve the outcomes in IRI when administered after the establishment of structural injury, raising the prospect of targeted cell therapy to support the function of the acutely injured kidney.
| S-EPMC2956932 | biostudies-literature