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

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.

Midkine is involved in kidney development and in its regulation by retinoids.

In the kidney, in which development depends on epithelial-mesenchymal interactions, it has been shown that retinoids modulate nephrogenesis in a dose-dependent manner in vivo and in vitro. Midkine (MK) is a retinoic acid responsive gene for a heparin-binding growth factor. The aim of the present study was therefore to quantify the expression of MK mRNA during renal development in the rat, to analyze the regulation of MK expression by retinoids in vivo and in vitro, and, finally, to study the role of MK in rat metanephric organ cultures.

Altered nephrogenesis due to maternal diabetes is associated with increased expression of IGF-II/mannose-6-phosphate receptor in the fetal kidney.

We have recently demonstrated that the exposure to hyperglycemia in utero impairs nephrogenesis in rat fetuses (Amri K et al., Diabetes 48:2240-2245, 1999). Diabetic pregnancy is commonly associated with alterations in the IGF system in fetal tissues.

Overexpression of human insulin-like growth factor binding protein-1 in the mouse leads to nephron deficit.

IGFs and their binding proteins are important regulators of fetal development. We have previously reported that overexpression of the human IGF binding protein-1 in mice is associated with glomerulosclerosis. The aim of this study was to investigate whether, in that model, decreased bioavailability of IGFs also affected nephrogenesis.

Retinoids and nephron mass control.

Advances in the molecular biology of retinoids have provided evidence that vitamin A profoundly influences the differentiation of the whole embryo. In addition to its well-characterized role in primary body axis and central nervous system formation, vitamin A is also required for the ad hoc development of numerous tissues and organs, including the kidney. This review will focus on the emerging evidence that the development of the urogenital tract depends on retinoids.