Mizoribine in the treatment of pediatric-onset glomerular disease
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Mizoribine in the treatment of pediatric-onset glomerular disease Hiroshi Tanaka, Kazushi Tsuruga, Taddatsu Imaizumi Hirosaki, Japan
Data Sources: In this review, we summarize reported possible benefits of MZR in the treatment of pediatriconset glomerular disease. Results: 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 balance and nephrin biogenesis in cultured podocyte and rat models, suggesting a direct anti-proteinuric effect of MZR.
Author Affiliations: Department of School Health Science, Faculty of Education, Hirosaki University, Hirosaki 036-8560, Japan (Tanaka H); Department of Pediatrics, Hirosaki University Hospital, Hirosaki 0368563, Japan (Tanaka H, Tsuruga K); Department of Vacular Biology, Graduate School of Medicine, Hirosaki University, Hirosaki 036-8562, Japan (Imaizumi T) Corresponding Author: Hiroshi Tanaka, MD, PhD, Department of School Health Science, Faculty of Education, Hirosaki University, 1 Bunkyo-cho, Hirosaki 036-8560, Japan (Email: [email protected]/hirotana@ hirosaki-u.ac.jp) doi: 10.1007/s12519-015-0013-7 ©Children's Hospital, Zhejiang University School of Medicine, China and Springer-Verlag Berlin Heidelberg 2015. All rights reserved.
World J Pediatr, Online First, March 2015 . www.wjpch.com
Conclusions: These beneficial mechanisms of action of MZR as well as its immunosuppressive effect would warrant its use in the treatment of pediatric-onset glomerular disease. Although further studies remain to be done, we believe that MZR may be an attractive treatment of choice for children with glomerular diseases from a histologic as well as clinical standpoint. World J Pediatr March 2015; Online First Key words: macrophage infiltration; mesangial cells; mizoribine; monocyte chemoattractant protein-1; podocytes
Introduction
M
izoribine (MZR), a purine synthesis inhibitor, was developed in Japan about 20 years ago. The mode of action of MZR is very similar to that of mycophenolate mofetil (MMF), involving selective inhibition of inosine monophosphate dehydrogenease (IMPD) in the pathway of de novo purine nucleotide synthesis, which results in the suppression of T and B lymphocyte proliferation.[1,2] So far, MZR has been used successfully without serious adverse effects in the treatment of renal transplant recipients,[3] nephrotic syndrome (NS), [4,5] immunoglobulin (Ig) A nephropathy,[6,7] and lupus nephritis (LN),[8,9] mainly in Japan and East Asia. In a previous experimental setting, MZ
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