Analysis of Molecular Mechanisms of Podocyte Injury and Its Prevention

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We have examined the molecular mechanisms of podocyte injury and found the 3 following results. 1) Mizoribine directly inhibits puromycin aminonucleoside-induced podocyte injury through the mechanism independent from IMPDH inhibition. 2) The mice that express mutant SIRP. lacking cytoplasmic region show flatted and irregularly arranged foot processes. In addition, the mutant mice are sensitive to diabetic nephropathy, suggesting that SIRP. and its downstream signalling pathway are involved in the progression of diabetic nephropathy. 3) TGF-β1 induces DNA methylation of WT1 promoter in cultured podocytes. However, the degree of DNA methylation was modest, suggesting that the possibility of methylation of the upstream region of that we have examined or methylation of the promoter of WT1-related molecules.