A5014066202- Liver Disease Diagnosis and Treatment
- Acute Kidney Injury Research
- Renal and related cancers
- Diet and metabolism studies
- Peroxisome Proliferator-Activated Receptors
- Polyomavirus and related diseases
- Adipose Tissue and Metabolism
- Mesenchymal stem cell research
- Diabetes Treatment and Management
- Renal Transplantation Outcomes and Treatments
- Lipoproteins and Cardiovascular Health
- Cancer-related molecular mechanisms research
- Extracellular vesicles in disease
- Mitochondrial Function and Pathology
- Cancer, Lipids, and Metabolism
- Chemotherapy-induced organ toxicity mitigation
- Cholesterol and Lipid Metabolism
- Lipid metabolism and disorders
- Metabolism, Diabetes, and Cancer
- Biomedical Ethics and Regulation
- Fatty Acid Research and Health
- Pancreatic function and diabetes
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Chemokine receptors and signaling
- Diet, Metabolism, and Disease
Amsterdam University Medical Centers
2023
University of Amsterdam
2005-2023
Netherlands Organisation for Applied Scientific Research
2022-2023
Netherlands Metabolomics Centre
2019-2023
Amsterdam UMC Location University of Amsterdam
2005-2018
Radboud University Nijmegen
2016
Nierstichting
2016
Radboud University Medical Center
2016
Centre for Human Drug Research
2010-2014
Leiden University
2010-2013
TLRs are conserved pattern recognition receptors that detect motifs of pathogens and host material released during injury. For unknown reasons, renal TLR2 mRNA is mainly expressed by tubular cells enhanced upon ischemia/reperfusion (I/R) We evaluated the role in I/R injury using TLR2-/- TLR2+/+ mice, antisense oligonucleotides, chimeric mice deficient leukocyte or TLR2. Tubular needed to produce significant cytokine chemokine amounts ischemia vitro. played a proinflammatory detrimental vivo...
Tubular epithelial injury represents an underestimated but important cause of renal dysfunction in patients with cholestasis and advanced liver disease, the underlying mechanisms are unclear. To address hypothesis that accumulation excessive alternative urinary elimination potentially toxic bile acids (BAs) may contribute to kidney cholestasis, we established a mouse model for detailed vivo time course as well treatment studies. Three-day common duct ligation (CBDL) induced tubular...
An accumulating body of evidence shows that gut microbiota fulfill an important role in health and disease by modulating local systemic immunity. The importance the microbiome development kidney disease, however, is largely unknown. To study this concept, we depleted with broad-spectrum antibiotics performed renal ischemia-reperfusion (I/R) injury mice. Depletion significantly attenuated damage, dysfunction, remote organ maintained tubular integrity after I/R injury. Gut flora–depleted mice...
Mitochondrial dysfunction is the most prominent source of oxidative stress in acute and chronic kidney disease. NLRX1 a receptor innate immune system that ubiquitously expressed localized mitochondria. We investigated whether may act at interface metabolism immunity model stress. Using chimeric mouse for renal ischemia-reperfusion injury, we found protects against mortality, mitochondrial damage, epithelial cell apoptosis an stress-dependent fashion. regulates phosphorylation integrity,...
Kidney ischemia/reperfusion injury (I/R) is characterized by renal dysfunction and tubular damages resulting from an early activation of innate immunity. Recently, nicotine administration has been shown to be a powerful inhibitor variety immune responses, including LPS-induced toxaemia. This cholinergic anti-inflammatory pathway acts via the α7 nicotinic acetylcholine receptor (α7nAChR). Herein, we tested potential protective effect in mouse model I/R induced bilateral clamping kidney...
Semaglutide, a glucagon-like peptide-1 receptor agonist, is an antidiabetic medication that has recently been approved for the treatment of obesity as well. Semaglutide postulated to be promising candidate non-alcoholic steatohepatitis (NASH). Here, Ldlr-/-.Leiden mice received fast-food diet (FFD) 25 weeks, followed by another 12 weeks on FFD with daily subcutaneous injections semaglutide or vehicle (control). Plasma parameters were evaluated, livers and hearts examined, hepatic...
Chemokines are important players in the migration of leukocytes to sites injury and also involved angiogenesis, development wound healing. In this study, we performed microarray analyses identify chemokines that play a role during inflammatory repair phase after renal ischemia/reperfusion (I/R) investigated temporal relationship between chemokine expression, leukocyte accumulation damage/repair. C57Bl/6 mice were subjected unilateral ischemia for 45 min sacrificed 3 h, 1 day 7 days...
Acute renal failure and tubular cell loss as a result of ischemia constitute major challenges in pathophysiology. Increasing evidence suggests important roles for bone marrow stem cells the regeneration tissue after injury. This study investigated whether enhanced availability hematopoietic cells, induced by factor granulocyte colony-stimulating factor, to injured kidney provides an adequate strategy cell-based therapy counteract ischemia/reperfusion It is interesting that cytokine treatment...
The chemokine stromal cell-derived factor-1 (SDF-1) is thought to be involved in mediating tissue repair by promoting migration of bone marrow stem or progenitor cells the site injury. Increased levels renal SDF-1 are found after kidney However, recently, we showed that does not play an important role haematopoietic post-ischaemic kidney. function increased expression modulating ischaemia/reperfusion injury remains, therefore, unknown.We studied locally decreasing and subsequent signalling...
Patients with metabolic syndrome are often prescribed statins to prevent the development of cardiovascular disease. Conversely, data on their effects non-alcoholic steatohepatitis (NASH) lacking. We evaluated these by feeding APOE*3-Leiden mice a Western-type diet (WTD) or without atorvastatin induce NASH and hepatic fibrosis. Besides well-known plasma cholesterol lowering (-30%) anti-atherogenic (severe lesion size -48%), significantly reduced steatosis (-22%), number aggregated...
Renal ischemia-reperfusion injury is associated with the loss of tubular epithelial cell-cell and cell-matrix interactions which contribute to renal failure. The Epac-Rap signaling pathway a potent regulator adhesion. cyclic AMP analogue 8-pCPT-2'-O-Me-cAMP has been shown selectively activate Epac, whereas addition an acetoxymethyl (AM) ester enhanced in vitro cellular uptake. Here we demonstrate that pharmacological activation using acetoxymethyl-8-pCPT-2'-O-Me-cAMP preserves cell adhesions...
Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibits the clearance of low-density lipoprotein (LDL) cholesterol (LDL-C) from plasma by directly binding with LDL receptor (LDLR) and sending for lysosomal degradation. As interaction promotes elevated LDL-C levels, therefore a predisposition to cardiovascular disease, PCSK9 has attracted intense interest as therapeutic target. Despite this interest, an orally bioavailable small-molecule inhibitor extensive lipid-lowering activity is...
BACKGROUND AND PURPOSE Nephrotoxicity is the principal dose‐limiting factor for cisplatin chemotherapy and primarily associated with proximal tubular epithelial cells, including disruption of cell adhesions induction apoptosis. Cell adhesion survival regulated by, amongst other factors, small GTPase Rap its activator, exchange protein directly activated by cAMP (Epac). Epac particularly enriched in renal tubule epithelium. This study investigates cytoprotective effects cAMP–Epac–Rap...
Activation of Rap1 by exchange protein activated cAMP (Epac) promotes cell adhesion and actin cytoskeletal polarization. Pharmacologic activation Epac-Rap signaling the Epac-selective analog 8-pCPT-2'-O-Me-cAMP during ischemia-reperfusion (IR) injury reduces renal failure application survival exposure to nephrotoxicant cisplatin. Here, we found that Epac reduced production reactive oxygen species reoxygenation after hypoxia decreasing mitochondrial superoxide production. prevented disruption...
NOD-like receptor (NLR)X1 (NLRX1) is an ubiquitously expressed inflammasome-independent NLR that uniquely localized in mitochondria with as yet unknown effects on metabolic diseases. Here, we report NLRX1 essential regulating cellular metabolism non-immune parenchymal hepatocytes by decreasing mitochondrial fatty acid-dependent oxidative phosphorylation (OXPHOS) and promoting glycolysis. loss mice has a profound impact the prevention of diet-induced syndrome parameters, non-alcoholic liver...
Background. Haematopoietic stem cells (HSC) have been shown to migrate the ischemic kidney. The factors that regulate trafficking of HSC damaged kidney are not fully understood. stromal cell-derived factor-1 (SDF-1)/CXCR4-axis has identified as central signalling axis regulating bone marrow. Therefore, we hypothesized SDF-1/CXCR4 interactions implicated in migration injured Methods. were isolated from mouse marrow and labelled with a cell tracker. Acceptor mice subjected unilateral ischemia...
Background Renal ischemia leads to apoptosis of tubular epithelial cells and results in decreased renal function. Tissue repair involves re-epithelialization the basement membrane. Survival epithelium following is therefore important successful regeneration tissue. The cytokine stem cell factor (SCF) has been shown protect against apoptosis. Methodology/Principal Findings In a mouse model for ischemia/reperfusion injury, we studied how expression c-KIT on its ligand SCF Administration...
Polyomavirus-associated nephropathy (PVAN) occurs in a significant percentage of renal transplant recipients, with BK virus reactivation as the main causative agent. PVAN leads to tubular damage and may result allograft loss. In this study, we analyzed antiviral immune response PVAN. Transcription proinflammatory cytokine interleukin-18 (IL-18) was significantly higher biopsies compared T cell-mediated rejection (TCMR) (1.42 ± 0.20 0.69 0.10, respectively; *P = 0.0021). Tubular expression...
While fibrosis stage predicts liver-associated mortality, cardiovascular disease (CVD) is still the major overall cause of mortality in patients with NASH. Novel NASH drugs should thus ideally reduce both liver and CVD. Icosabutate a semi-synthetic, liver-targeted eicosapentaenoic acid (EPA) derivative clinical development for The primary aims current studies were to establish anti-fibrotic anti-atherogenic efficacy icosabutate conjunction changes lipotoxic atherogenic lipids plasma...
The plasticity of bone marrow-derived stem cells, also comprising haematopoietic has been shown to extend renal epithelial lineages. Yet, the low rate their contribution injured kidney led questions regarding significance in tissue repair after acute injury. We describe here effect cell mobilization therapy on progression fibrosis a mouse model chronic obstructive nephropathy.Mice were subjected unilateral ureter obstruction (UUO) and treated with factor (SCF) granulocyte-colony stimulating...
Although both polyomavirus infection and T cell–mediated rejection (TCMR) are characterized by tubulointerstitial inflammation in the renal allograft, these conditions treated with opposing therapeutic regimens. To gain more insight into differences between antiviral alloimmune responses, we performed a case-control study, which immunophenotyped inflammatory infiltrates biopsy specimens BK polyomavirus–associated nephropathy (BKPyVAN) TCMR. Compared TCMR, BKPyVAN was diagnosed later after...
A gene-silencing platform (miQURE) has been developed and successfully used to deliver therapeutic microRNA (miRNA) the brain, reducing levels of neurodegenerative disease-causing proteins/RNAs via RNA interference improving disease phenotype in animal models. This study evaluates use miQURE technology miRNA for liver-specific indications. Angiopoietin-like 3 (ANGPTL3) was selected as target mRNA because it is produced liver loss-of-function ANGPTL3 mutations and/or pharmacological...