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- Title
Overexpression of thioredoxin1 in transgenic mice suppresses development of diabetic nephropathy.
- Authors
Yasuhiro Hamada; Satoshi Miyata; Tomoko Nii-Kono; Riko Kitazawa; Sohei Kitazawa; Satomi Higo; Michiru Fukunaga; Shigemitu Ueyama; Hajime Nakamura; Junji Yodoi; Masafumi Fukagawa; Masato Kasuga
- Abstract
Background. Oxidative stress has been suggested to play an important role in the pathogenesis of diabetic nephropathy. In the present study, the effects of thioredoxin1 (TRX1) overexpression, a small protein with antioxidant property, on the development of diabetic nephropathy in streptozotocin-induced diabetic animals were investigated using TRX1 transgenic mice (TRX1-Tg). Methods. Eight-week-old male TRX1-Tg and wild-type mice littermates (WT) mice were treated either with streptozotocin (200âmg/kg) or vehicle alone. After 24 weeks of treatment, diabetic nephropathy and oxidative stress were assessed in these four groups of mice, by biochemical analyses of blood and urine, as well as by histological analyses of the kidneys. Results. Haemoglobin A1c (HbA1c) levels of diabetic TRX1-Tg were not significantly different from those of the diabetic WT. Nevertheless, an augmented urinary albumin excretion observed in diabetic WT was significantly diminished in diabetic TRX1-Tg. Histological study revealed that pathological changes such as mesangial matrix expansion and tubular injury were significantly prevented in diabetic TRX1-Tg accompanied by a reduced tendency of expression of transforming growth factor-β as compared with diabetic WT. In parallel, urinary excretion of 8-hydroxy-2â²-deoxyguanosine and acrolein adduct and the immunostaining intensities of these markers in the kidney were significantly higher in diabetic WT compared with non-diabetic mice. The markers were significantly suppressed in diabetic TRX1-Tg, an indication of systemic and renal oxidative stress attenuation by TRX1 overexpression. Conclusion. These findings indicated the significant role of oxidative stress in the development of diabetic nephropathy and a potential inhibition of progression of nephropathy by TRX1.
- Subjects
KIDNEY diseases; THIOREDOXIN; OXIDATIVE stress; OXIDATION-reduction reaction
- Publication
Nephrology Dialysis Transplantation, 2007, Vol 22, Issue 6, p1547
- ISSN
0931-0509
- Publication type
Article
- DOI
10.1093/ndt/gfm099