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. 2010 Nov;1802(11):1020-7.
doi: 10.1016/j.bbadis.2010.07.004. Epub 2010 Jul 16.

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

Hanna Shevalye  1 , Yury Maksimchyk, Pierre Watcho, Irina G Obrosova
Affiliations

"VSports app下载" Poly(ADP-ribose) polymerase-1 (PARP-1) gene deficiency alleviates diabetic kidney disease

Hanna Shevalye et al. Biochim Biophys Acta. 2010 Nov.

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 12 weeks VSports手机版. 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. .

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Figures (V体育安卓版)

Fig. 1
Fig. 1
A) Representative Western blot analysis of renal cortex poly(ADP-ribose) polymerase-1 and B) poly(ADP-ribose)polymerase-1 content (densitometry), in control and diabetic wild-type and poly(ADP-ribose) polymerase-1-deficient mice. C – control; D – diabetic, PARP-1 – poly(ADP-ribose) polymerase-1. Mean ± SEM, n = 8–10 per group.
Fig. 2
Fig. 2
A) Representative Western blot analysis of renal cortex poly(ADP-ribosyl)ated proteins and B) poly(ADP-ribosyl)ated protein content (densitometry), in control and diabetic wild-type and poly(ADP-ribose)polymerase-1-deficient mice. C – control; D – diabetic, PARP-1 – poly(ADP-ribose) polymerase-1. Mean ± SEM, n = 9–12 per group. *, ** - p < 0.05 and < 0.01 vs corresponding non-diabetic groups.
Fig. 3
Fig. 3
A) Kidney weights and B) kidney weight-to-body weight ratios, in control and diabetic wild-type and poly(ADP-ribose)polymerase-1-deficient mice. C – control; D – diabetic, PARP-1 – poly(ADP-ribose) polymerase-1. Mean ± SEM, n = 10–15 per group. ** - p < 0.01 vs corresponding non-diabetic groups; ## - p < 0.01 vs diabetic wild-type mice.
Fig. 4
Fig. 4
A) Representative microphotographs and B) color intensities of PAS-positive substance stainings in the renal cortex in control and diabetic wild-type and poly(ADP-ribose)polymerase-1-deficient mice. C – control; D – diabetic, PARP-1 – poly(ADP-ribose) polymerase-1. Magnification x 400. Mean ± SEM, n = 10 per group. ** - p < 0.01 vs corresponding non-diabetic groups; # - p < 0.05 vs diabetic wild-type mice.
Fig. 5
Fig. 5
A) Representative Western blot analysis of renal cortex fibronectin and B) fibronectin content (densitometry), in control and diabetic wild-type and poly(ADP-ribose)polymerase-1-deficient mice. C – control; D – diabetic, PARP-1 – poly(ADP-ribose) polymerase-1. Mean ± SEM, n = 10–13 per group. *, ** - p < 0.05 and < 0.01 vs corresponding non-diabetic groups; ## - p < 0.01 vs diabetic wild-type mice.
Fig. 6
Fig. 6
A) Representative microphotographs of glomerular podocyte immunostaining and B) podocyte counts, in control and diabetic wild-type and poly(ADP-ribose)polymerase-1-deficient mice. C – control; D – diabetic, PARP-1 – poly(ADP-ribose) polymerase-1. Magnification x 400. Mean ± SEM, n = 10 per group. ** - p < 0.01 vs corresponding non-diabetic groups.
Fig. 7
Fig. 7
A) Transforming growth factor-β and B) nitrotyrosine concentrations, in the renal cortex in control and diabetic wild-type and poly(ADP-ribose)polymerase-1-deficient mice. C – control; D – diabetic, PARP-1 – poly(ADP-ribose) polymerase-1. Mean ± SEM, n = 9–14 per group. ** - p < 0.01 vs corresponding non-diabetic groups.
Fig. 8
Fig. 8
A) Representative microphotographs and B) percentage of positively stained for collagen area in the renal cortex in control and diabetic wild-type and poly(ADP-ribose)polymerase-1-deficient mice. C – control; D – diabetic, PARP-1 – poly(ADP-ribose) polymerase-1. Magnification x 200. Mean ± SEM, n = 8–10 per group. ** - p < 0.01 vs corresponding non-diabetic groups; ## - p < 0.01 vs diabetic wild-type mice.
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