Several months back I posted something on hepcidin--the 25 amino acid peptide secreted by the liver which appears to be the "master regulator" of iron metabolism, and whose levels appear to be perhaps increased in ESRD patients, providing a possible explanation for the anemia of chronic kidney disease.Hemojuvelin is a protein which has recently been identified as a critical regulator of hepcidin, and thus also likely an important player in anemia of chronic kidney disease. Clues as to hemojuvelin's function comes from children with mutations in this gene, which result in severe juvenile-onset hemochromatosis (as evidenced from the positive Prussian blue staining of a liver biopsy specimen, shown above left).
Hemojuvelin turns out to be a co-receptor, acting at the plasma membrane, for the BMP signaling pathway, which is necessary for the secretion of hepcidin from hepatocytes. As elevated hepcidin levels are associated with anemia of chronic disease and decreased access to reticuloendothelial stores, it stands to reason that inhibitors of the BMP pathway--either small molecule BMP inhibitors such as this, or a soluble form of hemojuvelin such as this--might be successfully used to decrease hepcidin expression and therefore treat anemia of chronic kidney disease.
ALSO: Be the coolest kid on the block to know the Top 10 Nephrology Stories of 2008 according to the Precious Bodily Fluids nephrology blog!
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