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Insulin-like growth factor (IGF) and IGF binding protein gene expression in multicystic renal dysplasia
D G Matsell1, T Bennett, R A Armstrong
1Department of Pediatrics, University of Western Ontario, London, Canada.
Insights
Multicystic dysplastic kidney disease involves abnormal kidney development and histopathology. Altered insulin-like growth factor (IGF) and IGF binding protein (IGFBP) expression suggests a role in this condition.
Area of Science:
- Developmental biology
- Pediatric nephrology
- Molecular pathology
Background:
- Multicystic dysplastic kidney disease (MCDK) is the leading cause of end-stage renal disease (ESRD) in children.
- MCDK involves abnormal kidney development, leading to cysts and impaired function.
Purpose of the Study:
- To describe the histopathological changes in MCDK from fetal to postnatal life.
- To investigate the expression of insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs) in MCDK.
Main Methods:
- Histopathological examination of MCDK kidneys across developmental stages.
- Analysis of mRNA expression for IGF-II, IGFBP-2, and IGFBP-3 using techniques like in situ hybridization.
Main Results:
- Early cystic changes and displaced metanephric blastema were observed at 14 weeks gestation.
- Later stages showed cyst enlargement, fibromuscular collars, and disorganized mesenchymal tissue.
- IGF-II and IGFBP-2 were overexpressed in abnormal tissues throughout development, with IGF-II localized to fibromuscular collars and IGFBP-2 to cyst epithelia.
- IGFBP-3 mRNA was absent from cyst epithelia.
Conclusions:
- Normal IGF expression is disrupted in MCDK development.
- The IGF system likely plays a role in the progressive histopathological changes observed in MCDK.
Abstract:
Multicystic dysplastic kidney disease is the most common form of renal dysplasia that leads to ESRD in children. This study describes the histopathological changes of multicystic dysplasia that occur from early fetal life to the postnatal period. At 14 wk gestation, early cystic enlargement of various segments of the nephron have been identified, in addition to a displaced metanephric blastema adjacent to zones of normal nephrogenesis. At later stages, the predominant features include cyst enlargement with marked fibromuscular collars, architectural disorganization, and replacement of the interstitium with a disarray of mesenchymal tissue. This study investigated the expression of the mRNA encoding the insulin-like growth factors (IGF) and IGF binding proteins (IGFBP) and have demonstrated IGF-II, IGFBP-2, and IGFBP-3 to be altered. Apart from their expression in the displaced metanephric blastema, both IGF-II and IGFBP-2 were overexpressed in abnormal tissue elements in all kidneys from fetal to postnatal life. IGF-II gene expression was localized to mesenchymal tissue, specifically in the periductal fibromuscular collars. IGFBP-2 mRNA was found to be expressed exclusively in the cyst epithelia of all cysts at all ages studied, whereas IGFBP-3 mRNA was absent from these epithelia. This study details the failure of normal IGF expression in the development of multicystic renal dysplasia and suggests a role for the IGF system in the progressive histopathological changes of this disorder.