Strain differences rather than hyperglycemia determine the severity of glomerulosclerosis in mice

Feng Zheng, Gary E. Striker, Ciro Esposito, Enrico Lupia, Liliane J. Striker

Research output: Contribution to journalArticle

Abstract

Background. We reported that ROP, but not C57, mice were prone to glomerulosclerosis (GS) after nephron reduction (J Clin Invest 97:1242, 1996). Methods. In this study, we induced diabetes in ROP and C57 mice to determine if the glomerulosclerotic response was stimulus specific. We used the oligosyndactyly mutation (Os), to produce a congenital 50% reduction in nephron number. Stable hyperglycemia was induced by streptozotocin and mice were maintained for 12 weeks without insulin treatment. Results. Glomerular hypertrophy occurred in diabetic ROP +/+ and C57 +/+ mice, but glomeruli of diabetic ROP +/+ mice had 1.92-fold higher laminin B1 and 1.5-fold higher tenascin mRNA levels than diabetic C57 +/+ mice. Diabetic ROP Os/+ mice had severe glomerulosclerosis with arteriolar and tubulointerstitial lesions while there was only moderate mesangial sclerosis in diabetic C57 Os/+ mice. Glomerular size was increased in all non-diabetic Os/+ mice. It was further increased in diabetic ROP Os/+ mice, but not in diabetic C57 Os/+ mice. Glomerular mRNA levels were higher in diabetic ROP OS/+ than in diabetic C57 OS/+ mice [α1 (IV) collagen 3.2-fold, laminin B1 2.1-fold, and tenascin 1.6- fold]. Conclusion. Overall, our data further support the hypothesis that the susceptibility to glomerulosclerosis is inherited, and suggest that hyperglycemia serves principally as a triggering event in the development of diabetic nephropathy. Since the acceleration of diabetic nephropathy by nephron reduction was also largely strain dependent, it appears that the propensity to glomerulosclerosis is a general renal response and is not stimulus specific.

Original languageEnglish
Pages (from-to)1999-2007
Number of pages9
JournalKidney International
Volume54
Issue number6
DOIs
Publication statusPublished - 1998

Keywords

  • Diabetes
  • Glomerular lesions
  • Insulin
  • Nephropathy
  • Sclerosis
  • Susceptibility to GS

ASJC Scopus subject areas

  • Nephrology

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