Wednesday, January 27, 2010

IN THE NEWS- HIF and Kidney Disease

A recent article in Kidney International talks about the hypoxia inducible factor or HIF and its relation to kidney diseases and anemia.  Based on recent basic science experiments done on AKI and podocytopathies, it has been found that there are different variants of HIF 1 Alpha and 2 Alpha respectively affecting different parts of the kidney.  This paper is one of first basic science papers to localize HIF 2Alpha.  Accumulation of HIF 2Alpha was observed in mainly endothelial and glomerular cells whereas HIF 1Alpha was more in the tubular epithelia. This was more speculative before but now its confirmed.  A large proportion of erythropoetin expressing cells also co expressed HIF 2Alpha.  No co relation with Hif1alpha was found.

Why is this important?  In hypoxic challenges, there is stimulus to produce HIFs and that might be a stimulus for EPO production as well.  Hif is a protein that has alpha and beta subunits,  In normoxemia, Hif Alpha is always synthesized.  However, steady state levels are low as Hif is rapidly ubiquitinated and degraded. This degradation happens via the action of hif with Von Hippel lindau protein (vhL).  In hypoxemia, this interaction is suppressed and you have increased Hif production leading to accumulation in the cells.
This leads to downstream effects of increased Epo and expression of different types of hifs in different parts of kidneys. Hif1 in tubular cells perhaps during AKI
Hif 2 in podocytes and endothelial cells perhaps in glomerular injury
Interestingly , another down stream protein to Hif is VEGF..
A lot of things might be falling into place soon!!
The picture on the left ( Univ of Adelaide courtesy) can explain a lot

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