Poly(ADP-ribose) polymerase-1 (PARP-1) gene deficiency alleviates diabetic kidney disease.
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-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.
Shevalye
Hanna
H
Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA.
Maksimchyk
Yury
Y
Watcho
Pierre
P
Obrosova
Irina G
IG
D000419:Albuminuria / Q000652:urine; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D004797:Enzyme-Linked Immunosorbent Assay; D006984:Hypertrophy / Q000097:blood / Q000209:etiology / Q000652:urine; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D007674:Kidney Diseases / Q000201:enzymology* / Q000209:etiology / Q000235:genetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D050199:Podocytes / Q000473:pathology; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000172:deficiency* / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D001786:Blood Glucose; D053773:Transforming Growth Factor beta1; C002744:3-nitrotyrosine; D014443:Tyrosine; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases