Experimentelle Nephropathologie

The "ET" Lab

Endothelin-1 (ET-1) is a major transcriptional activator of renal proximal tubule cells acting in an autocrine and paracrine manner and has been implicated in progressive renal interstitial fibrosis by promoting gene expression, via different signal pathway.

Therefore, our research effort has focussed on the role of ET-1 in progressive renal diseases and renal tumors. This resulted in the description of a normal signalling pathway via the ETA-receptor and a cytoplasmic transcription complex consisting NF-kB p65, MAPK p38 and PKCα migrating into the nucleus, which has been analysed in normal and tumoral proximal tubular cells and renal tumors (see figure below).

Our group is especially interested in the involvement of ET-1 in different kidney diseases predominantly triggered via the proximal tubular cells.

A further research interest focused on the ET-1 induced regulation of microRNAs (miRNAs) and their role in the development of kidney tumors and other kidney diseases. With respect to the miRNAs, we were able to detect a miRNA, called miRNA 15a, which is only upregulated in urine samples from patients with clear cell renal carcinoma and this upregulation disappears after tumor removal.

This resulted in recognition by the Walter Schulz Stiftungspreis in 2012

Awards

2011

  • Young Investigator Awards, Endothelin-1 Conference,  Cambridge, UK,  to Dr. M. von Brandenstein and MSc M. Schlosser
  • Award for best oral presentation, Endothelin-1 Conference Cambridge, UK, to Dr. M. von Brandenstein
  • Award for best poster presentation, Endothelin-1 Conference Cambridge, UK, to Dr. M. von Brandenstein

2012

  • Walter Schulz Forschungspreis to Dr. M. von Brandenstein

2013

  • Young Investigator Awards, Endothelin-1 Conference,  Tokio, Japan,  to Dr. H. Löser, BSc Julia Straube and Dr. M. von Brandenstein

Monica Schlosser, M. Sc.

Financial support

Prof. Dr. Joachim W.U. Fries

  • Marga und Walter Boll Stiftung,
  • Private donations,
  • Köln Fortune,
  • Imhoff-Stiftung

Dr. Heike Löser

  • Köln Fortune 

Dr. rer. medic. Melanie Freifrau von Brandenstein

  • Köln Fortune,
  • 2nd Professorinnenprogramm der Universität zu Köln,
  • Wiedereinstiegsprogramm der Universität zu Köln, Exzellent Research Support Programm

M. Schlosser  MSc

  • Wiedereinstiegsprogramm der Universität zu Köln, Exzellent Research Support Programm
Publications

Melanie Gerstung, Tanja Roth, Hans-Peter Dienes, Christoph Licht, Jochen W U Fries, Endothelin-1 induces NF-kappaB via two independent pathways in human renal tubular epithelial cells. American Journal of Nephrology 2007, Vol. 27, Issue 3, 294-300

Melanie Gerstung von Brandenstein, Anna Ngum Abety, Reinhard Depping, Tanja Roth, Matthias Koehler, Hans-Peter Dienes, Jochen W U Fries, A p38-p65 transcription complex induced by endothelin-1 mediates signal transduction in cancer cells. Biochemica et Biophysica Acta (BBA)- Molecular Cell Research 2008, Vol. 1783, Issue 9, 1613-1622

M von Brandenstein, R Depping, H-P Dienes, J W U Fries, Endothelin-1 induced Protein kinase C αregulates nuclear pri-microRNA 15a release, Biochim Biophys Acta. 2011 Oct;1813(10):1793-802.

Melanie von BrandensteinJency J. PandarakalamLukas KroonHeike LoeserJan Herden, Gabriele BraunKatherina WendlandHans P. DienesUdo EngelmannJochen W.U. Fries, MicroRNA 15a, Inversely Correlated to PKCα, Is a Potential Marker to Differentiate between Benign and Malignant Renal Tumors in Biopsy and Urine Samples, The American Journal of Pathology,Volume 180, Issue 5, May 2012, Pages 1787–1797

Melanie von BrandensteinClaudia RichterJochen W.U. Fries, MicroRNAs: Small but amazing, and their association with endothelin, Life SciencesVolume 91, Issues 13–14, 15 October 2012, Pages 475–489

von Brandenstein MSchlosser MRichter CDepping RFries JWU, ETS-dependent p16INK4a and p21waf1/cip1 gene expression upon endothelin-1 stimulation in malignant versus and non-malignant proximal tubule cells, Life Scinces, 2012 Oct 15;91(13-14):562-71

H Loeser, M von Brandenstein, A Herschung,  M Schlosser, Buettner R, JWU Fries Endothelin-1 influences Multiple Drug Resistance in the human renal proximal tubule via microRNA 133a downregulating the MRP2 transporter, Life Scinces, under review

Es besteht eine enge Kooperation mit der Nephrologischen Forschungsgruppe Prof. Benzing et al.

Klinik II für Innere Medizin - Nephrologie, Rheumatologie, Diabetologie und Allgemeine Innere Medizin

Nach oben scrollen