A5043660512- Renal Diseases and Glomerulopathies
- Chronic Kidney Disease and Diabetes
- Renal and related cancers
- Genetic and Kidney Cyst Diseases
- Cell Adhesion Molecules Research
- Autoimmune Bullous Skin Diseases
- Pancreatic function and diabetes
- Reproductive Biology and Fertility
- Dialysis and Renal Disease Management
- Platelet Disorders and Treatments
- Wnt/β-catenin signaling in development and cancer
- Acute Kidney Injury Research
- Lymphatic System and Diseases
- Hippo pathway signaling and YAP/TAZ
- Erythrocyte Function and Pathophysiology
- Renal cell carcinoma treatment
- Mast cells and histamine
- CRISPR and Genetic Engineering
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Systemic Lupus Erythematosus Research
- Complement system in diseases
- Vasculitis and related conditions
- Biomedical Research and Pathophysiology
- Tissue Engineering and Regenerative Medicine
- Lymphatic Disorders and Treatments
RWTH Aachen University
2015-2024
Universitätsklinikum Aachen
2014-2024
Radboud University Nijmegen
2008-2022
Radboud University Medical Center
2022
Westfälische Hochschule
2007-2021
Health & Life (Taiwan)
2020-2021
Suzuki (Japan)
2020-2021
Center for Translational Molecular Medicine
2020-2021
Délégation Paris 6
2020-2021
Cancer Genetics (United States)
2020-2021
Loss of a critical number podocytes from the glomerular tuft leads to glomerulosclerosis. Even in health, some are lost into urine. Because themselves cannot regenerate, we postulated that parietal epithelial cells (PECs), which proliferate throughout life and adjoin podocytes, may migrate differentiate podocytes. Here, describe transitional at vascular stalk exhibit features both PECs Metabolic labeling juvenile rats suggested become To prove this, generated triple-transgenic mice allowed...
The Kidney Disease: Improving Global Outcomes (KDIGO) initiative organized a Controversies Conference on glomerular diseases in November 2017. conference focused the 2012 KDIGO guideline with aim of identifying new insights into nomenclature, pathogenesis, diagnostic work-up, and, particular, therapy since guideline's publication. It was consensus group that most recommendations, particular those dealing therapy, will need to be revisited by guideline-updating Work Group. This report covers...
Regeneration of injured tubular cells occurs after acute necrosis primarily from intrinsic renal cells. This may occur a pre-existing intratubular stem/progenitor cell population or any surviving proximal cell. In this study, we characterize CD24-, CD133-, and vimentin-positive subpopulation scattered throughout the tubule in normal human kidney. Compared to adjacent 'normal' cells, these CD24-positive contained less cytoplasm, fewer mitochondria, no brush border. addition, 49 marker...
In November 2017, the Kidney Disease: Improving Global Outcomes (KDIGO) initiative brought a diverse panel of experts in glomerular diseases together to discuss 2012 KDIGO glomerulonephritis guideline context new developments and insights that had occurred over years since its publication. During this Controversies Conference on Glomerular Diseases, group examined data disease pathogenesis, biomarkers, treatments identify areas consensus controversy. This report summarizes discussions...
Abstract Summary: We report a transgenic mouse line that expresses Cre recombinase exclusively in podocytes. Twenty‐ four founders were generated which was placed under the regulation of 2.5‐kb fragment human NPHS2 promoter. Previously, this shown to drive beta‐galactosidase (β‐gal) expression podocytes mice. For analysis, founder mice bred with ROSA26 mice, reporter β‐gal cells undergo recombination. Eight 24 lines found express kidney. Histological analysis kidneys showed confined...
Cellular lesions form in Bowman's space both crescentic glomerulonephritis and collapsing glomerulopathy. The pathomechanism origin of the proliferating cells these are unknown. In this study, we examined by lineage tracing either podocytes or parietal epithelial (PECs) nephrotoxic nephritis model inflammatory glomerulonephritis. addition, traced fate genetically labeled PECs Thy-1.1 transgenic mouse models, cellular bridges composed were observed between capsule glomerular tuft. Genetically...
The pathogenesis of the development sclerotic lesions in focal segmental glomerulosclerosis (FSGS) remains unknown. Here, we selectively tagged podocytes or parietal epithelial cells (PECs) to determine whether PECs contribute sclerosis. In three distinct models FSGS (5/6-nephrectomy + DOCA-salt; murine transgenic chronic Thy1.1 model; MWF rat) and human biopsies, primary injury induce associated with activation formation cellular adhesions capillary tuft. From this entry site, activated...
ABSTRACT. Cellular crescents are a defining histologic finding in many forms of inflammatory glomerulonephritis. Despite numerous studies, the origin glomerular remains unresolved. A genetic cell lineage-mapping study with novel transgenic mouse model was performed to investigate whether visceral epithelial cells, termed podocytes, precursors cells that populate cellular crescents. The podocyte-specific 2.5P-Cre line crossed ROSA26 reporter line, resulting irreversible constitutive...
Podocyte loss is a major determinant of progressive CKD. Although recent studies showed that subset parietal epithelial cells can serve as podocyte progenitors, the role turnover and regeneration in repair, aging, nephron remains unclear. Here, we combined genetic fate mapping with highly efficient isolation protocols to precisely quantify regeneration. We demonstrate give rise fully differentiated visceral indistinguishable from resident podocytes limited renewal occurs diphtheria toxin...
Alterations in glomerular podocyte cell-cell and cell-matrix contacts are key events progressive failure. Integrin-linked kinase (ILK) has been implicated interaction is induced proteinuria. For evaluation of ILK function vivo, mice with a Cre-mediated podocyte-specific inactivation were generated. These seemed normal at birth but developed focal segmental glomerulosclerosis died terminal renal The first ultrastructural lesions that seen onset albuminuria basement membrane (GBM) alterations...
Abstract Endoplasmic reticulum (ER) stress is associated with diabetic nephropathy (DN), but its pathophysiological relevance and the mechanisms that compromise adaptive ER signalling in podocytes remain unknown. Here we show nuclear translocation of transcription factor spliced X-box binding protein-1 (sXBP1) selectively impaired DN, inducing activating factor-6 (ATF6) C/EBP homology protein (CHOP). Podocyte-specific genetic ablation XBP1 or inducible expression ATF6 mice aggravates DN....
Spatial organization of cells and their appendages is controlled by the planar cell polarity pathway, a signaling cascade initiated protocadherin Fat in Drosophila. Vertebrates express 4 molecules, Fat1-4. We found that depletion Fat1 caused cyst formation zebrafish pronephros. Knockdown PDZ domain containing adaptor protein Scribble intensified cyst-promoting phenotype depletion, suggesting act overlapping cascades during pronephros development. Supporting genetic interaction with Fat1,...
Significance Acute kidney injury (AKI) is a common and significant clinical problem for which no specific therapy has been developed. There controversy about the origin of regenerating tubular cells after AKI. Attention recently focused on “scattered cells” (STCs), are by far best candidate postulated fixed progenitor population cells. In present study, we clarify this question genetic cell fate labeling using unique transgenic mouse. We show that STCs may arise from any these do not...
Recent data suggest that the chemokine receptor CXCR3 is functionally involved in fibroproliferative disorders, including liver fibrosis. Neoangiogenesis an important pathophysiological feature of scarring, but a functional role angiostatic chemokines this process unclear. We therefore investigated neoangiogenesis carbon tetrachloride (CCl(4))-induced fibrosis Cxcr3(-/-) and wildtype mice by histological, molecular, imaging methods. Furthermore, we assessed direct vascular endothelial growth...
Under physiologic conditions, significant amounts of plasma protein pass the renal filter and are reabsorbed by proximal tubular cells, but it is not clear whether endocytosed protein, particularly albumin, degraded in lysosomes or returned to circulatory system intact. To resolve this question, a transgenic mouse with podocyte-specific expression doxycycline-inducible tagged murine albumin was developed. assess potential glomerular backfiltration, two types different charges were expressed....
Podocyte loss is key in glomerulosclerosis. Activated parietal epithelial cells are proposed to contribute pathogenesis of glomerulosclerosis and may serve as stem that can transition podocytes. CD44 a marker for activated cells. This study investigated whether increased early recurrent FSGS transplant compared with minimal change disease.CD44 staining renal allograft biopsies from 12 patients was performed native kidneys disease or normal control without FSGS. CD44+ along Bowman's capsule...
Previously, we showed that some podocytes in juvenile mice are recruited from cells lining Bowman's capsule, suggesting parietal epithelial (PECs) a progenitor cell population for podocytes. To investigate whether PECs also replenish adult mice, were genetically labeled an irreversible fashion 5-week-old mice. No significant increase was observed, even after 18 months. accelerate potential regenerative mechanism, progressive glomerular hypertrophy induced by partial nephrectomies. Again, no...
The cellular origins of glomerulosclerosis involve activation parietal epithelial cells (PECs) and progressive podocyte depletion. While mammalian target rapamycin-mediated (mTOR-mediated) hypertrophy is recognized as an important signaling pathway in the context glomerular disease, role a compensatory mechanism preventing PEC remains poorly understood. In this study, we show that mTOR activation-related genes were both upregulated intercorrelated biopsies from patients with focal segmental...
Carnosinase 1 (CN1) is a secreted dipeptidase that hydrolyzes L-carnosine. Recently, we have identified an allelic variant of human CN1 (hCN1) results in increased enzyme activity and associated with susceptibility for diabetic nephropathy patients. We therefore hypothesized L-carnosine the serum represents critical protective factor patients.L-carnosine levels were manipulated db/db mice, model type 2 diabetes. In transgenic approach, hCN1 cDNA was expressed under control liver-specific...