A5051916941- Renin-Angiotensin System Studies
- Genetic and Kidney Cyst Diseases
- Retinal Diseases and Treatments
- Hormonal Regulation and Hypertension
- Receptor Mechanisms and Signaling
- Renal and related cancers
- Retinal Development and Disorders
- Angiogenesis and VEGF in Cancer
- Renal Diseases and Glomerulopathies
- Neuroinflammation and Neurodegeneration Mechanisms
- Biomedical Research and Pathophysiology
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Hedgehog Signaling Pathway Studies
- Animal Genetics and Reproduction
- Lipid metabolism and disorders
- Advanced Glycation End Products research
- Retinal Imaging and Analysis
- Protease and Inhibitor Mechanisms
- Diabetes and associated disorders
- Mast cells and histamine
- Circadian rhythm and melatonin
- Genetic Syndromes and Imprinting
- Nuclear Receptors and Signaling
- Ion Channels and Receptors
- Mitochondrial Function and Pathology
Heidelberg University
2013-2025
Novartis Institutes for BioMedical Research
2024
Novartis (Switzerland)
2024
University Medical Centre Mannheim
2011-2022
University Hospital Heidelberg
2012-2022
Central Institute of Mental Health
2016
LMU Klinikum
2011
Ludwig-Maximilians-Universität München
2011
Olgahospital
2011
Medizinische Fakultät Mannheim
2010
The mechanism underlying pericyte loss during incipient diabetic retinopathy remains controversial. Hyperglycemia induces angiopoietin-2 (Ang-2) transcription, which modulates capillary coverage. In this study, we assessed of subgroups and the contribution Ang-2 to migration.Numbers total pericytes their were quantified in retinal digest preparations spontaneous XLacZ mice. Pericytes divided into according localization, position relative adjacent endothelial cells, expression LacZ. migration...
Angiotensin II (AngII) is a critical determinant of glomerular function involving both hemodynamic and pressure-independent effects that are insufficiently understood. A novel transgenic rat (TGR) model with overexpression the human AngII type 1 receptor (hAT1) in podocytes was developed to study consequences an increased AT1 signaling on structure filter. Use nephrin promoter target resulted expression hAT1 at level roughly two times higher than endogenous throughout life. All male TGR...
Progressive kidney diseases are often associated with scarring of the kidney's filtration unit, a condition called focal segmental glomerulosclerosis (FSGS). This is due to loss podocytes, cells critical for glomerular filtration, and leads proteinuria failure. Inherited forms FSGS caused by Rac1-activating mutations, Rac1 induces TRPC5 ion channel activity cytoskeletal remodeling in podocytes. Whether mediates onset progression unknown. We identified small molecule, AC1903, that...
Angiopoietin-2 (Ang2) is among the relevant growth factors induced by hypoxia and plays an important role in initiation of retinal neovascularizations. Ang2 also involved incipient diabetic retinopathy, as it may cause pericyte loss. To investigate impact on developmental hypoxia-induced angiogenesis, we used a transgenic mouse line overexpressing human retina. Transgenic mice displayed reduced coverage capillaries with pericytes (-14%; p < 0.01) 46% increase vascular density capillary...
To evaluate the cardiovascular actions of kinins, we established a transgenic rat line harboring human tissue kallikrein gene, TGR(hKLK1). Under control zinc-inducible metallothionein promoter, transgene was expressed in most tissues including heart, kidney, lung, and brain, detected urine animals. Transgenic rats had lower 24-h mean arterial pressure comparison with rats, which further decreased when their diet supplemented zinc. The day/night rhythm blood significantly diminished...
Abstract Immunity to Toxoplasma gondii critically depends on TNFR type I-mediated immune reactions, but the precise role of individual ligands TNFR1, TNF and lymphotoxin-α (LTα), is still unknown. Upon oral infection with T. gondii, TNF−/−, LTα−/−, TNF/LTα−/− mice failed control intracerebral succumbed an acute necrotizing encephalitis, whereas wild-type (WT) survived. Intracerebral inducible NO synthase expression and–early after infection–splenic levels were reduced. Additionally,...
Abstract —The plasma membrane calmodulin–dependent calcium ATPase (PMCA) is a calcium-extruding enzyme controlling Ca 2+ homeostasis in nonexcitable cells. However, its function the myocardium unclear because of presence Na + /Ca exchanger. We approached question physiological pump using transgenic “gain function” model. Transgenic rat lines carrying human PMCA 4 cDNA under control ventricle-specific myosin light chain-2 promoter were established, and expression was ascertained at mRNA,...
Autosomal dominant polycystic kidney disease (PKD) is the most common genetic that leads to failure in humans. In addition known causative genes PKD1 and PKD2, there are mutations result cystic changes kidney, such as nephronophthisis, autosomal recessive disease, or medullary disease. Recent efforts improve understanding of renal cystogenesis have been greatly enhanced by studies rodent models PKD. Genetic (cy/+) rat showed PKD spontaneously develops a consequence mutation gene different...
Neuronal damage is correlated with vascular dysfunction in the diseased retina, but underlying mechanisms remain controversial because of lack suitable models which vasoregression related to neuronal initiates mature retinal vasculature. The aim this study was assess temporal link between and patency a transgenic rat (TGR) overexpression mutant cilia gene polycystin-2.Vasoregression, neuroglial changes expression neurotrophic factors were assessed TGR control rats time course. Determination...
Background and aims. In diabetic kidney disease models, carnosine supplementation ameliorates renal pathology, but its influence in other pathologies is less explored. Thus, using the transgenic rat TGRNeph-hAT1 with sex-dependent focal segmental glomerulosclerosis we first tested whether expression levels of system components correlate disease. Next, assessed male rats improves pathology. Methods. 10-week-old phenotypically healthy female TGRNeph-hAT1, compared by qRT-PCR. were supplemented...
The cloning of the PKD1 and PKD2 genes has led to promising new insight into mechanisms that are responsible for cyst development in patients with autosomal dominant polycystic kidney disease. Although pattern inheritance would argue haploinsufficiency, a gain function, or negative mechanism, there is good evidence disease behaves like recessive on cellular level (two-hit mechanism cystogenesis). For testing whether other pathomechanisms addition two-hit hypothesis can explain formation, two...
Renin transcripts lacking exon 1 and thus the signal sequence for co-translational transport to endoplasmatic reticulum encode a protein (exon[2-9]renin), that is confined cytoplasm. The function of exon(2-9)renin currently unknown. Mitochondrial renin increases under conditions which stimulate aldosterone production. We hypothesized (1) translated into functionally active in vivo, (2) not secreted but remains within cytoplasm (3) stimulates To test these hypotheses we generated transgenic...
Vasoregression is a hallmark of vascular eye diseases but the mechanisms involved are still largely unknown. We have recently characterized rat ciliopathy model which develops primary photoreceptor degeneration and secondary vasoregression. To improve understanding vasoregression in retinal neurodegeneration, we used microarray techniques to compare gene expression profiles this new before after Differential was validated by quantitative RT-PCR, Western blot immunofluorescence. Of 157 genes...
Podocytes have a significant role in establishing selective permeability of the glomerular filtration barrier. Sustained renin-angiotensin-aldosterone system activation is crucial to pathogenesis podocyte injury, but mechanisms by which angiotensin II modulates survival due physiological or injurious stimuli remain unclear. Here, we used proteomic analysis find new mediators II-induced injury. Antioxidant protein peroxiredoxin 2 expression was decreased cultured podocytes stimulated with II....
Rats expressing a transgenic polycystic kidney disease (PKD) gene develop photoreceptor degeneration and subsequent vasoregression, as well activation of retinal microglia macroglia. To target the whole neuroglialvascular unit, neuro- vasoprotective Erythropoietin (EPO) was intraperitoneally injected into four –week old male heterozygous PKD rats three times week at dose 256 IU/kg body weight. For comparison EPO-like peptide, lacking unwanted side effects EPO treatment, given five 10 µg/kg...
It is currently controversially discussed whether mesenchymal stem cells (MSC) facilitate cartilage regeneration in vivo by a progenitor- or nonprogenitor-mediated mechanism. Here, we describe potentially novel unbiased cell tracking system based on transgenic donor and corresponding immunocompetent marker-tolerant recipient mouse rat lines inbred genetic backgrounds. Tolerance of recipients was achieved expression an immunologically neutral but physicochemically distinguishable variant the...