title: Senescence marker protein-30/gluconolactonase deficiency exacerbates diabetic nephropathy through tubular injury in a mouse model of type 1 diabetes.
abstract: OBJECTIVE
  Senescence marker protein-30 (SMP30) is abundantly expressed in renal proximal tubule cells, but its expression decreases with age. Previous studies have shown that reduced SMP30 expression could contribute to aging-associated deterioration of cellular function and tissue injury. In the present study, we investigated the effects of SMP30 deficiency on the pathogenesis of diabetic nephropathy.
  
  
  METHODS
  Diabetes was induced using streptozotocin in male SMP30 knockout mice (KO) and wild-type mice at 7 weeks-of-age. Vitamin C was added to the drinking water to prevent vitamin C deficiency in KO mice. The mice were killed 12 weeks after the induction of diabetes.
  
  
  RESULTS
  Urinary biomarkers for proximal tubule damage were significantly increased in non-diabetic KO mice compared with wild-type mice. Furthermore, diabetes-induced tubular damage was significantly exacerbated by SMP30 deletion. Morphological analysis showed a link between cortical tubulointerstitial fibrosis area and the degree of tubular damage. However, SMP30 deletion did not affect mesangial expansion. Tubular injury was associated with accumulation of hypoxia-inducible factor-1α and increased hypoxia-inducible factor-1α targeted gene expression. SMP30 deletion initiated oxidative stress; however, it did not exacerbate the oxidative stress seen in diabetic mice. In contrast, tubular inflammation was associated with SMP30 deletion only in diabetic mice.
  
  
  CONCLUSIONS
  Based on this evidence, we concluded that SMP30 deficiency exacerbates proximal tubule injury in diabetic mice. Decreased SMP30 could contribute to the increased incidence of various chronic kidney diseases, including diabetic nephropathy, with age.
authors.affiliation: Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science Kyoto, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Okada
authors.affiliation: Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science Kyoto, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Senmaru
authors.affiliation: Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science Kyoto, Japan.
authors.forename: Michiaki
authors.initials: M
authors.lastname: Fukui
authors.affiliation: Molecular Regulation of Aging, Tokyo Metropolitan Institute of Gerontology Tokyo, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Kondo
authors.affiliation: Molecular Regulation of Aging, Tokyo Metropolitan Institute of Gerontology Tokyo, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Ishigami
authors.affiliation: Molecular Regulation of Aging, Tokyo Metropolitan Institute of Gerontology Tokyo, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Maruyama
authors.affiliation: Institute of Bio-Response Informatics Kyoto, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Obayashi
authors.affiliation: Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science Kyoto, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamazaki
authors.affiliation: Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science Kyoto, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Nakamura
authors.affiliation: Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science Kyoto, Japan.
authors.forename: Goji
authors.initials: G
authors.lastname: Hasegawa
keywords: Diabetic nephropathy; Senescence marker protein-30; Tubular injury