Seminar: Prof. Kai-Uwe Eckardt

Erythropoietin – still an elusive hormone?

Date:
8 January 2014 00:00 hrs.
Location:
Figdor Lecture Theatre, 8th floor RIMLS Building, Geert Grooteplein 26-28, route 289
Title:
Erythropoietin – still an elusive hormone?
Speaker(s):

Prof. Kai-Uwe Eckardt, department of Nephrology and Hypertension, Universitätsklinikum, Erlangen, Germany

Host(s):

Prof. Peter Deen, department of Physiology, Radboudumc

08-01-2014 00:00:00Europe/AmsterdamErythropoietin – still an elusive hormone? Figdor Lecture Theatre, 8th floor RIMLS Building, Geert Grooteplein 26-28, route 289Rimlsrimls@radboudumc.nl

Remarks / more information:

 

MMD Course: Oxygen in health and disease

Eckardt , Kai -UweApproximately 100 years ago, high altitude physiologists described an increase in the number of circulating red blood cells as a characteristic component of adaptation to high altitude. While it was originally assumed that red blood cell precursors in the bone marrow respond directly to changes in oxygen tensions, subsequent elegant animal studies provided proof for a circulating hormone that was subsequently termed "erythropoietin" and identified as being produced primarily by the kidney. The sites and mechanisms of its production and mode of regulation remained elusive for many decades. During the last 20 years major progress has been achieved. Peritubular interstitial fibroblasts in the renal cortex were identified as the cellular sites of erythropoietin production. On a molecular level, hypoxia inducible transcription factors were discovered as protein regulators of erythropoietin gene transcription. There are at least 2 different isoforms, HIF-1α and HIF-2α, but HIF-2α appears critical for erythropoietin regulation. Degradation of HIF in the presence of oxygen is mediated by the von-Hippel-Lindau protein complex. As a consequence of that, genetic or acquired modifications in the von-Hippel-Lindau protein can result in HIF stabilization and the clinical syndrome of polycythemia. Despite significant increase in the understanding of erythropoietin regulation, many important questions still remain unanswered. In particular, it is still unclear why erythropoietin production is inadequately low in patients with chronic kidney disease, although it is frequently assumed that hypoxia is an important characteristic of progressive kidney disease.



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