Developmental Gene Expressed With Diabetic Nephropathy

Expression of gremlin, a gene involved in nephrogenesis, may not end after embryonic development and can reemerge in the context of diabetic nephropathy. Dr. Vincent Dolan, of University College Dublin, and colleagues evaluated gremlin expression in normal human adult kidneys and in kidneys with diabetic nephropathy.

Gremlin expression was not seen in the normal kidneys, whereas abundant expression was observed in the nephropathic kidneys, the investigators note. Further analysis revealed that gremlin expression was primarily confined to areas of tubulointerstitial fibrosis, typically in association with the expression of transforming growth factor-beta.

Although gremlin mRNA levels did not correlate with the degree of proteinuria, they were directly linked with the level of renal dysfunction, the authors note. Moreover, gremlin expression was strongly associated with the tubulointerstitial fibrosis score.
"Considered with reports from other investigators highlighting the prominence of gremlin expression in fibroblast cultures, these data suggest a role for gremlin in the pathogenesis of tubulointerstitial fibrosis," the researchers state. As such, gremlin could serve as a target for therapeutic intervention, they add.

Am J Kidney Dis 2005;45:1034-1039.

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