A5074632025- Genetic and Kidney Cyst Diseases
- Biomedical Research and Pathophysiology
- Microtubule and mitosis dynamics
- Ion Transport and Channel Regulation
- Aquatic Ecosystems and Phytoplankton Dynamics
- Micro and Nano Robotics
- Electrolyte and hormonal disorders
- Protist diversity and phylogeny
- Renal Diseases and Glomerulopathies
- Pelvic and Acetabular Injuries
- Hernia repair and management
- Renal and related cancers
- Amino Acid Enzymes and Metabolism
- Hip and Femur Fractures
- Epigenetics and DNA Methylation
- Photoreceptor and optogenetics research
- Endoplasmic Reticulum Stress and Disease
- Microbial Community Ecology and Physiology
Friedrich-Alexander-Universität Erlangen-Nürnberg
2019-2024
Bayer (Germany)
2019-2024
Yale University
2021-2024
Kantonsspital Winterthur
2021
Abstract Aim In nephrotic syndrome, aberrantly filtered plasminogen (plg) is converted to active plasmin by tubular urokinase‐type activator (uPA) and thought lead sodium retention proteolytic activation of the epithelial channel (ENaC). This concept predicts that uPA an important factor for inhibition might be protective in syndrome. Methods Activation amiloride‐sensitive currents plg were studied Xenopus laevis oocytes expressing murine ENaC. doxorubicin‐induced mice, was inhibited...
Abstract Proteolytic activation of the epithelial sodium channel (ENaC) by aberrantly filtered serine proteases is thought to contribute renal retention in nephrotic syndrome. However, identity responsible remains elusive. This study evaluated factor VII activating protease (FSAP) as a candidate this context. We analyzed FSAP urine patients with syndrome and mice investigated its ability activate human ENaC expressed Xenopus laevis oocytes. Moreover, we studied FSAP-deficient ( Habp2 −/− )...
Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic cause of chronic and fourth leading end-stage disease, accounting for over 50% prevalent cases requiring renal replacement therapy. There a pressing need improved therapy ADPKD. Recent insights into pathophysiology ADPKD revealed that cyst cells undergo metabolic changes up-regulate aerobic glycolysis in lieu mitochondrial respiration energy production, process ostensibly fuels their increased proliferation....
Significance Statement XBP1 activation in neonatal and adult doxycycline-inducible murine models of ADPKD due to a hypomorphic polycystin-1 missense mutation orthologous human PC1R2220W delays cyst formation. Activating XBP1s, pro-chaperone inducer the endoplasmic reticulum stress response, can improve steady-state expression, ciliary trafficking, cleavage mutant protein, providing initial vivo proof concept that modulating levels poorly functioning PC1 alleles slow progression kidney...
Background: Since diagnosis-related groups (SwissDRG) were established in Switzerland 2012, small and medium-size hospitals have encountered increasing financial troubles. Even though hernia repair operations are frequent, most fail to cover their costs with these procedures. Previous studies focused mainly on analyzing the contributing factors but less variables that can be positively influenced. Therefore, this study aims identify relevant influenceable for revenue growth surgery. Methods:...
Autosomal-dominant polycystic kidney disease (ADPKD) is caused by mutations affecting polycystin-1 (PC1) or polycystin-2 (PC2). Recent structural data suggest that PC1 and PC2 can form heterotetrameric ion channels with a 3:1 stoichiometry, the channel in closed state. In this hetero-oligomeric formation three residues (R4100, R4107, H4111) would work together two (L677, N681) to block permeation pathway. Here, we provide functional evidence supporting model. When pore-blocking are replaced...
ABSTRACT Mutations in the PKD2 gene cause autosomal-dominant polycystic kidney disease but physiological role of polycystin-2, protein product PKD2, remains elusive. Polycystin-2 belongs to transient receptor potential (TRP) family non-selective cation channels. To test hypothesis that altered ion channel properties polycystin-2 compromise its putative a control circuit controlling lumen formation renal tubular structures, we generated mouse model which exchanged pore loop with closely...
Geiges, Linda; Staudner, Tobias; Korbmacher, Christoph; Ilyaskin, Alexandr V. Author Information
Staudner, Tobias; Geiges, Linda; Korbmacher, Christoph; Ilyaskin, Alexandr V. Author Information
Background: Autosomal dominant polycystic kidney disease (ADPKD) is an incurable genetic affecting over 500,000 people in the United States and 12 million worldwide. If untreated, ADPKD can lead to end-stage failure about 50% of patients by age 60, which underscores significant need for therapies that slow down progression while preserving function. The present work describes a small-molecule therapeutic strategy cyst cells are selectively targeted apoptosis.Methods: A compound denoted...