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Spatiotemporal distribution of insulin-like growth factor receptors during nephrogenesis in fetuses from normal and diabetic rats

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Abstract

Exposure to hyperglycemia in utero impairs rat nephrogenesis. The effect of maternal diabetes on insulin-like growth factors and their receptors in the fetal kidney is associated with an increase in both mRNA and protein of the insulin-like growth factor II/mannose 6-phosphate receptor. However, this receptor has never been localized in the fetal kidney. The spatial and temporal distribution of the three insulin-like growth factor receptors (insulin-like growth factor I receptor, insulin-like growth factor II/mannose 6-phosphate receptor and insulin receptor) in rat metanephros during both normal and streptozotocin-induced diabetic renal development was investigated using in situ hybridization and immunohistochemistry. All receptors were found in the fetal kidney from the start of nephrogenesis. Insulin-like growth factor I receptor expression was ubiquitous and continuously present during metanephric development. Insulin receptor expression was developmentally regulated during kidney maturation with an enhanced expression in proximal tubules at the late stages of development. Insulin-like growth factor II/mannose 6-phosphate receptor expression was ubiquitous in the early stages of development and was dramatically decreased at the late stages of normal kidney development. Insulin receptor and insulin-like growth factor I receptor expressions were unchanged in diabetic metanephroi. Although the spatial expression of insulin-like growth factor II/mannose 6-phosphate receptor was unaffected by hyperglycemia, its expression was not downregulated in the mesenchyme of the nephrogenic zone of diabetic fetuses on gestational day 20. This study suggests a crucial role of insulin-like growth factor II/mannose 6-phosphate receptor in the pathogenesis of the impaired nephrogenesis in fetuses of diabetic mothers.

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Acknowledgements

We thank Drs. Haugel, Clément, Maître, and MacDonald for kindly providing specific probes and antibodies.

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Authors and Affiliations

  1. INSERM U430, IFR 58, Hôpital Broussais, Paris, France

    J.-P. Duong Van Huyen, M.-F. Bélair & P. Bruneval

  2. INSERM U356, IFR 58, Centre de recherches biomédicales des Cordeliers, Paris, France

    K. Amri, J. Vilar, C. Merlet-Bénichou & M. Lelièvre-Pégorier

  3. Department of Pathology, Hôpital Européen Georges Pompidou, Paris, France

    J.-P. Duong Van Huyen & P. Bruneval

  4. Laboratoire d’Anatomie Pathologique, Hôpital Européen Georges Pompidou, 20–40 rue Leblanc, 75015, Paris, France

    J.-P. Duong Van Huyen

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  1. J.-P. Duong Van Huyen
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Correspondence to J.-P. Duong Van Huyen.

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Duong Van Huyen, JP., Amri, K., Bélair, MF. et al. Spatiotemporal distribution of insulin-like growth factor receptors during nephrogenesis in fetuses from normal and diabetic rats. Cell Tissue Res 314, 367–379 (2003). https://doi.org/10.1007/s00441-003-0803-4

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  • DOI: https://doi.org/10.1007/s00441-003-0803-4

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