A5057903428- Chronic Kidney Disease and Diabetes
- Renal Diseases and Glomerulopathies
- Hormonal Regulation and Hypertension
- Vasculitis and related conditions
- Renin-Angiotensin System Studies
- Acute Kidney Injury Research
- Dialysis and Renal Disease Management
- Pregnancy and preeclampsia studies
- Phagocytosis and Immune Regulation
- Birth, Development, and Health
- Complement system in diseases
- Organ Transplantation Techniques and Outcomes
- Congenital heart defects research
- Angiogenesis and VEGF in Cancer
- Eicosanoids and Hypertension Pharmacology
- Barrier Structure and Function Studies
- Neurological Disease Mechanisms and Treatments
- Cell Adhesion Molecules Research
- Renal Transplantation Outcomes and Treatments
- Connexins and lens biology
- Osteoarthritis Treatment and Mechanisms
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Otitis Media and Relapsing Polychondritis
- Heme Oxygenase-1 and Carbon Monoxide
- Renal and related cancers
Medizinische Hochschule Hannover
2008-2018
RELX Group (United States)
2018
Hypertension Institute
2015
Mount Desert Island Biological Laboratory
2002-2013
Jackson Laboratory
2013
Brigham and Women's Hospital
2013
Charité - Universitätsmedizin Berlin
2001-2012
RWTH Aachen University
2008-2012
Max Delbrück Center
2000-2012
Xiamen Tungsten (China)
2012
The hematopoietic cytokine erythropoietin has cytoprotective effects in endothelial cells vitro that are mediated through direct activation of the pro-survival Akt tyrosine kinase signaling pathway. We tested hypothesis low-dose therapy with long-acting recombinant human analogue darbepoetin alpha protects vascular endothelium vivo a classic remnant kidney rat model characterized by severe damage, progressive sclerosis, and ischemia-induced tissue fibrosis.Using parallel group study design,...
Activation of protein kinase C (PKC) isoforms has been implicated in the pathogenesis diabetic nephropathy. We showed earlier that PKC-α is activated kidneys hyperglycemic animals. now used PKC-α−/− mice to test hypothesis this PKC isoform mediates streptozotocin-induced observed renal and glomerular hypertrophy was similar wild-type mice. However, development albuminuria almost absent The hyperglycemia-induced downregulation negatively charged basement membrane heparan sulfate proteoglycan...
Objective. Endothelial cells play a central pathogenetic role in ANCA-associated small-vessel vasculitis (AAV). Circulating endothelial (CECs), as marker of damage, have been shown to be elevated vasculitis. More recently, microparticles (EMPs) were found increased active childhood The EMP adult AAV and the relationship between CEC is unclear. Patients methods. We studied 26 patients with AAV, 12 healthy volunteers 10 IgA nephropathy disease control. Platelet-poor plasma was...
Angiopoietin-2, a protein secreted by stimulated endothelium and an antagonist of the endothelium-stabilizing receptor Tie2, contributes to pathophysiology septic multiple organ dysfunction. We tested therapeutic potential pulmonary-endothelium-specific RNA interference-based angiopoietin-2 targeting strategy in sepsis.Laboratory animal research.Research laboratories Medical School Hannover, Department Nephrology Hypertension, Hannover Silence Therapeutics GmbH, Berlin.C57Bl/6...
ABSTRACT. The mammalian kidney responds to partial nephrectomy with glomerular and tubular hypertrophy, but without renal regeneration. In contrast, regeneration in lower vertebrates is known occur. Understanding the underlying mechanisms of highly important; however, a serviceable animal model has not been developed. A neonephrogenic zone identified European lesser spotted dogfish, Scyliorhinus caniculus (Hentschel H. Am J Anat 190: 309–333, 1991), as well spiny dogfish Squalus acanthias...
The protein kinase C (PKC)-β isoform has been implicated to play a pivotal role in the development of diabetic kidney disease. We tested this hypothesis by inducing nephropathy PKC-β–deficient (PKC-β−/−) mice. studied nondiabetic and streptozotocin-induced PKC-β−/− mice compared with appropriate 129/SV wild-type After 8 weeks diabetes, high-glucose–induced renal glomerular hypertrophy, as well increased expression extracellular matrix proteins such collagen fibronectin, was reduced...
Albuminuria in diabetic nephropathy is due to endothelial dysfunction, a loss of negative charges the basement membrane, and changes slit-membrane diaphragm composition. We have recently shown that protein kinase C alpha (PKCalpha)-deficient mice are protected against development albuminuria under conditions. here tested hypothesis PKCalpha mediates hyperglycemia-induced downregulation slit-diaphragm nephrin. After 8 weeks streptozotocin (STZ)-induced hyperglycemia expression glomerular...
CD4+ T cells contribute to the pathogenesis of ischemia-reperfusion injury, which is primary cause delayed graft failure after kidney transplantation. The TIM-1:TIM-4 pathway participates in activation/differentiation cells, suggesting that it may modulate injury. Here, we studied role TIM-1 a murine uninephrectomized renal injury model. Blocking with an antagonistic monoclonal antibody protected function and diminished reperfusion resulting from 30 minutes ischemia. Histologic examination...
Protein kinase C (PKC), a family of 12 distinct serine-threonine kinases, is an important intracellular signaling pathway involved in various cellular functions, such as proliferation, hypertrophy, apoptosis, and adhesion. PKC-epsilon, novel PKC isoform that activated the diabetic kidney, has been demonstrated to have central role underlying infrastructure myocardial ischemia hypertrophy. The renal phenotype PKC-epsilon(-/-) mice was studied with regard hypertrophy fibrosis. deficient...
Mineralocorticoid receptor blockade protects from angiotensin II-induced target-organ damage. 11beta-Hydroxysteroid dehydrogenase type 2 the mineralocorticoid activation by glucocorticoids; however, high glucocorticoid concentrations and absent 11beta-hydroxysteroid in some tissues make glucocorticoids highly relevant ligands. We investigated effects of corticosterone (10(-6) to 10(-12) mol/L) on early vascular signaling Western blotting, confocal microscopy, myography. Corticosterone...
Abstract Background Endothelial tight and adherens junctions control a variety of physiological processes like adhesion, paracellular transport solutes or trafficking activated leukocytes. Formation maintenance endothelial largely depend on the microenvironment specific vascular bed interactions endothelium with adjacent cell types. Consequently, primary cultures cells often lose their junctional pattern fail to establish monolayer in vitro . This is also true for isolated from vein human...
ANCA-associated vasculitides are characterized by inflammatory destruction of small vessels accompanied enhanced cleavage membrane-bound proteins. One the main proteases responsible for ectodomain shedding is disintegrin and metalloproteinase domain-containing protein 17 (ADAM17). Given its potential role in aggravating vascular dysfunction, we examined ADAM17 active proteinase-3 (PR3)-positive vasculitis (AAV). concentration was significantly increased plasma samples from patients with...
Acute kidney injury (AKI) increases the risk of morbidity and mortality after major surgery transplantation. We investigated effect PKC-ε deficiency on AKI ischemic allograft damage PKC-ε-deficient wild type (WT) control mice were subjected to 35 min renal pedicle clamping induce AKI. was associated with a marked improvement in survival an attenuated loss function. Furthermore, functional MRI experiments revealed better perfusion than WT one day IRI. tubular necrosis neutrophil infiltration...
About one-half of double transgenic rats (dTGR) overexpressing the human renin and angiotensinogen genes die by age 7 wk terminal heart failure (THF); other (preterminal) develop cardiac damage but survive. Our study's aim was to elucidate gene expression differences in dTGR-THF compared with dTGR showing compensated hypertrophy not yet THF. treated losartan (LOS) nontransgenic (SD) served as controls. THF-dTGR body weight significantly lower than for all groups. At death, had blood...
Central mechanisms leading to ischemia induced allograft rejection are apoptosis and inflammation, processes highly regulated by the urokinase-type plasminogen activator (uPA) its specific receptor (uPAR). Recently, up-regulation of uPA uPAR has been shown correlate with in human biopsies. However, causal connection uPA/uPAR mediating transplant underlying molecular remain poorly understood. In this study, we evaluated role a mice model for kidney reperfusion (IR) injury acute rejection. but...
Interstitial fibrosis and tubular atrophy (IF/TA) in renal transplants are the major morphological correlates of progressive graft deterioration. Early diagnosis IF/TA is a pre-requisite for timely therapeutic intervention patients at risk. To evaluate events occurring before overt onset IF/TA, gene expression profiling 3-month protocol biopsies from with was performed patient group (n = 8) who developed mild [chronic allograft nephropathy (CAN) grade I, by Banff scoring system] subsequent...
Aldosterone (Aldo) is involved in vascular remodeling and inflammation; however, the mechanisms are imperfectly defined. We hypothesized that Aldo alters endothelial integrity modifies paracellular permeability. Human umbilical vein cells were exposed to (10(-9) mol/L) alterations permeability, assembly of tight adherens junctions activation intracellular signaling pathways determined. increased permeability for molecules ≤ 70 kDa within 60 minutes. A transient loss cortical actin with...