Poly(ADP-ribose) polymerase-1 (PARP-1) gene deficiency alleviates diabetic kidney disease

Hanna Shevalye , Yury Maksimchyk , Pierre Watcho , Irina G. Obrosova

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 12 weeks. 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-β 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.

Mots clés: Albuminuria; collagen; diabetic nephropathy; mesangial expansion; poly(ADP-ribose) polymerase-1; poly(ADP-ribose)polymerase-1 deficient mouse; renal podocyte

Hanna Shevalye, Yury Maksimchyk, Pierre Watcho, Irina G. Obrosova. Poly(ADP-ribose) polymerase-1 (PARP-1) gene deficiency alleviates diabetic kidney disease. Biochimica et Biophysica Acta - Molecular Basis of Disease, 2010, 1802 (11), pp.1020. ⟨10.1016/j.bbadis.2010.07.004⟩. ⟨hal-00623313⟩