title: Overexpression of thioredoxin1 in transgenic mice suppresses development of diabetic nephropathy.
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 (200 mg/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-beta as compared with diabetic WT. In parallel, urinary excretion of 8-hydroxy-2'-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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Diabetes, Digestive and Kidney Diseases, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hamada
authors.forename: Satoshi
authors.initials: S
authors.lastname: Miyata
authors.forename: Tomoko
authors.initials: T
authors.lastname: Nii-Kono
authors.forename: Riko
authors.initials: R
authors.lastname: Kitazawa
authors.forename: Sohei
authors.initials: S
authors.lastname: Kitazawa
authors.forename: Satomi
authors.initials: S
authors.lastname: Higo
authors.forename: Michiru
authors.initials: M
authors.lastname: Fukunaga
authors.forename: Shigemitu
authors.initials: S
authors.lastname: Ueyama
authors.forename: Hajime
authors.initials: H
authors.lastname: Nakamura
authors.forename: Junji
authors.initials: J
authors.lastname: Yodoi
authors.forename: Masafumi
authors.initials: M
authors.lastname: Fukagawa
authors.forename: Masato
authors.initials: M
authors.lastname: Kasuga
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003928:Diabetic Nephropathies / Q000235:genetics* / Q000378:metabolism / Q000517:prevention & control*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018384:Oxidative Stress / Q000235:genetics; D013879:Thioredoxins / Q000096:biosynthesis* / Q000235:genetics*
chemical_list: C515559:Txn1 protein, mouse; D013879:Thioredoxins