부산대학교 도서관

Abstract: Poly(ADP-ribose)polymerase (PARP) inhibitors prevent or alleviate diabetic nephropathy. This study evaluated the role for PARP-1 in diabetic kidney disease using the PARP-1-deficient mouse. PARP-1−/− and the wild-type (129S1/SvImJ) mice were made diabetic with streptozotocin, and were maintained for 12weeks. Final blood glucose concentrations were increased ∼3.7-fold in both diabetic groups. PARP-1 protein expression (Western blot analysis) in the renal cortex was similar in non-diabetic and diabetic wild-type mice (100% and 107%) whereas all knockouts were PARP-1-negative. PARP-1 gene deficiency reduced urinary albumin (ELISA) and protein excretion prevented diabetes-induced kidney hypertrophy, and decreased mesangial expansion and collagen deposition (both assessed by histochemistry) as well as fibronectin expression. Renal podocyte loss (immunohistochemistry) and nitrotyrosine and transforming growth factor-β1 accumulations (both by ELISA) were slightly lower in diabetic PARP-1−/− mice, but the differences with diabetic wild-type group did not achieve statistical significance. In conclusion, PARP-1−/− gene deficiency alleviates although does not completely prevent diabetic kidney disease. [Copyright &y& Elsevier]