Glomerulosclerosis in mice transgenic for human insulin-like growth factor-binding protein-1

Sophie Doublier, Danielle Seurin, Bruno Fouqueray, Marie Christine Verpont, Patrice Callard, Liliane J. Striker, Gary E. Striker, Michel Binoux, Laurent Baud

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Background. The growth hormone (GH)/insulin-like growth factor (IGF) system is thought to participate in the glomerulosclerosis process. Because IGF-binding proteins (IGFBPs) modulate IGF actions and hence GH secretion, this study assessed whether mice transgenic for human IGFBP-1 have altered susceptibility to glomerulosclerosis. Methods. A line of transgenic mice that express human IGFBP-1 mRNA in the liver under the control of the α1- antitrypsin promoter has been obtained, and morphological changes in the kidney tissue were assessed. Glomerulosclerosis was identified using light microscopy, light microscopic morphometry, and electron microscopy. Extracellular matrix components were analyzed by immunohistochemistry. Results. There was a marked increase in mesangial extracellular matrix area in homozygous transgenic mice at three months of age as compared with heterozygous transgenic mice and nontransgenic littermates. These changes were not associated with alterations in glomerular volume or cellularity. The expansion of extracellular matrix area was related to a marked increase in laminin and type IV collagen and to the appearance of type I collagen. Conclusions. These observations indicate that the enhanced expression of IGFBP-1 may result in the development of glomerulosclerosis without glomerular hypertrophy. The changes are potentially related to a decrease in IGF-I availability and/or to an IGF-I-independent role of IGFBP-1.

Original languageEnglish
Pages (from-to)2299-2307
Number of pages9
JournalKidney International
Volume57
Issue number6
DOIs
StatePublished - 2000
Externally publishedYes

Keywords

  • Chronic renal failure
  • Glomerular extracellular matrix
  • Growth hormone
  • Insulin-like growth factor
  • Progressive glomerulosclerosis

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