Glomerulosclerosis in mice transgenic for human insulin-like growth factor-binding protein-1
| Autor: | Liliane J. Striker, Gary E. Striker, Danielle Seurin, Marie-Christine Verpont, Michel Binoux, Sophie Doublier, Bruno Fouqueray, Laurent Baud, Patrice Callard |
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| Rok vydání: | 2000 |
| Předmět: |
Genetically modified mouse
medicine.medical_specialty glomerular extracellular matrix medicine.medical_treatment Kidney Glomerulus Blood Pressure Mice Transgenic Biology Kidney insulin-like growth factor Mice Type IV collagen Insulin-like growth factor chronic renal failure Laminin Internal medicine medicine Animals Humans Urea Glomerulosclerosis Focal Segmental Growth factor Body Weight Glomerulosclerosis Organ Size medicine.disease Growth hormone secretion Insulin-Like Growth Factor Binding Protein 1 Proteinuria Endocrinology progressive glomerulosclerosis Nephrology Creatinine Growth Hormone biology.protein Disease Susceptibility Type I collagen |
| Zdroj: | Kidney International. 57(6):2299-2307 |
| ISSN: | 0085-2538 |
| DOI: | 10.1046/j.1523-1755.2000.00090.x |
| Popis: | Glomerulosclerosis in mice transgenic for human insulin-like growth factor-binding protein-1. 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. |
| Databáze: | OpenAIRE |
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