Role of CTGF on podocytes and tubulointerstitium in chronic kidney disease.

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CTGF is a growth factor strongly induced by TGF-β and has a profibrotic effects. Neonatal death of CTGF knockout mice by the deformity of the ribs makes the evaluation of the role of CTGF in chronic kidney disease difficult. To solve these problems, we constructed CTGF floxed mice. We generated systemic inducible CTGF knockdown mice and podocyte-specific CTGF knockout mice to investigate the role of CTGF in chronic kidney disease.1. Systemic tamoxifen inducible CTGF knockdown mice.We crossed RosaCreER^<T2> mice, which activate Cre recombinase by the stimulation of tamoxifen, with CTGF floxed mice to generate systemic inducible CTGF knockdown mice. Although expression of CTGF in the kidney, liver and heart of systemic inducible CTGF knockdown mice is reduced by 80-90%, histological examination showed normal phenotype. Gene array were performed to find candidate gene on the CTGF-downstream pathway.2. Diabetic nephropathy in podocyte-specific CTGF knockout mice.We generated podocyte-specific CTGF knockout mice. Although expression of CTGF mRNA in glomeruli was decreased by 87%, the kidney was normal and urinary albumin excretion was within normal range. Next, we generated type 1 diabetic mice by injection of streptozotocin in podocyte-specific CTGF knockout mice. There is no significant difference between diabetic wild-type mice and diabetic podocyte-specific CTGF knockout mice in urinary albumin excretion and renal histology.