Mizoribine in the treatment of pediatric-onset glomerular disease
Abstract
Mizoribine (MZR) is a selective inhibitor of inosine monophosphate dehydrogenase, a key enzyme in the pathway responsible for de novo synthesis of guanine nucleotides. As an immunosuppressant, MZR has been used successfully without any serious adverse effects in the treatment of renal diseases in children as well as adults. Besides its immunosuppressive effect, MZR has been reported to ameliorate tubulointerstitial fibrosis in rats via suppression of macrophage infiltration. In this review, we summarize reported possible benefits of MZR in the treatment of pediatriconset glomerular disease. We recently observed that MZR itself selectively attenuates the expression of monocyte chemoattractant protein-1 at both the mRNA and protein levels in human mesangial cells. Since MZR binds specifically to 14-3-3 proteins and heat shock protein 60, both of which are reportedly expressed in inflamed glomeruli, MZR may bind directly to inflamed glomerular cells, thereby possibly preventing progressive damage from glomerulonephritis through a suppressive effect on activated macrophages and intrinsic renal cells. Moreover, it has recently been reported that MZR directly prevents podocyte injury through correction of the intracellular energy bal...Continue Reading
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