Project Details
FOR 667: Epithelial Mechanisms in Renal Volume Regulation
Subject Area
Medicine
Term
from 2005 to 2017
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 16133448
The kidneys filter a daily input of 1500 liters of blood and produce 180 liters of primary ultrafiltrate. The ultrafiltrate becomes elaborated by the renal tubule until the final formation of 1.5 liters of urine. Specific activities of the tubular epithelium help to perform this major task of the kidney. In the tubule, filtered ions and water are being reabsorbed. In addition, many compounds are transported in- and outwards according to the momentary requirements to be recovered by the circulation, or excreted into the urine. Body sodium and water balance are importantly regulated by renal mechanisms which help to keep plasma osmolality within tight limits irrespective of the wide variations in dietary salt and water uptake. The control of sodium balance and the adjustment of blood pressure depend on each other.
It has been known for many years that impaired kidney function may cause hyper- or hypotension. Approximately one third of the German polulation suffers from hypertension which may lead to congestive heart failure and stroke. The kidney itself may as well be affected secondarily. The regulatory processes which cause maladaptation of renal ion and water balance have not been well understood until now.
We therefore initiated the Research Unit consortium in order to synergistically investigate basic science aspects and pathophysiological mechanisms in renal epithelial transport functions involving group members from Charité - Universitätsmedizin Berlin, Max-Delbrück-Center for Molecular Medicine (MDC), Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin-Buch, and the Zentrum für Molekulare Neurobiologie in Hamburg (ZMNH). Together we aim at increasing our knowledge on specific ion exchanger, channel, and cotransport proteins, and products they interact with. The transporters are regulated by cellular signal transduction cascades triggered by tubular ion composition and hormonal stimuli. Their movements within the cell by trafficking and translocation, their localisation in the membrane and within cell organelles will be studied in function of the different portions of the nephron. Pathophysiologically relevant alterations of the kidney such as proteinuria, eventually leading to renal failure and volume disorder, will be studied with respect to their impact on epithelial transport.
It has been known for many years that impaired kidney function may cause hyper- or hypotension. Approximately one third of the German polulation suffers from hypertension which may lead to congestive heart failure and stroke. The kidney itself may as well be affected secondarily. The regulatory processes which cause maladaptation of renal ion and water balance have not been well understood until now.
We therefore initiated the Research Unit consortium in order to synergistically investigate basic science aspects and pathophysiological mechanisms in renal epithelial transport functions involving group members from Charité - Universitätsmedizin Berlin, Max-Delbrück-Center for Molecular Medicine (MDC), Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin-Buch, and the Zentrum für Molekulare Neurobiologie in Hamburg (ZMNH). Together we aim at increasing our knowledge on specific ion exchanger, channel, and cotransport proteins, and products they interact with. The transporters are regulated by cellular signal transduction cascades triggered by tubular ion composition and hormonal stimuli. Their movements within the cell by trafficking and translocation, their localisation in the membrane and within cell organelles will be studied in function of the different portions of the nephron. Pathophysiologically relevant alterations of the kidney such as proteinuria, eventually leading to renal failure and volume disorder, will be studied with respect to their impact on epithelial transport.
DFG Programme
Research Units
International Connection
Switzerland
Projects
- Bedeutung des proteinurischen Tubulusharns bei Dysfunktion des transepithelialen Natriumtransports (Applicant Theilig, Franziska )
- Dissektion der Rolle von CIC-5 und anderen vesikulären CLCs bei der renalen Endozytose und tubulären Transportprozessen (Applicant Jentsch, Thomas J. )
- Funktion des osmo-regulierten Kationenkanals TRPV4 in der Niere (Applicant Harteneck, Christian )
- Identifizierung und Charakterisierung von Proteinen, die den Transport von von Aquaporin-2 in renalen Hauptzellen kontrollieren (Applicant Klußmann, Enno )
- Posttranskriptionelle Kontrolle der Synthese des Na-Kanal-Proteins EnaC (Applicant Thiele, Bernd-Joachim )
- Rolle des Sorting-Rezeptors SORLA in der funktionellen Aktivierung von NKCCD2 (Applicant Willnow, Thomas E. )
- Rolle des tubulären Renin-Angiotensin- und Kallikrein-Kinin-Systems in der Nierenfunktion und bei Hypertonie-bedingter Nephropathie (Applicant Bader, Michael )
- Untersuchung der Rolle des Transkriptionsfaktors grainyhead-like 2 (Grhl2) bei der transkriptionellen Regulation von Komponenten des apikalen junktionalen Komplexes in Sammelrohrepithelien der Niere (Applicant Schmidt-Ott, Kai )
- Untersuchungen zur Biologie des Kationen-Chlorid-Kotransporters in der aufsteigenden Schleife der Säugerniere (Applicant Bachmann, Sebastian )
- Zentrale Mittel (Applicant Bachmann, Sebastian )
Spokesperson
Professor Dr. Sebastian Bachmann