EXPRESSION OF INSULIN-LIKE GROWTH-FACTOR AND BINDING-PROTEIN GENES DURING NEPHROGENESIS

To study the role of insulin-like growth factors (IGFs) and their bind ing proteins (IGFBPs) in human nephrogenesis, we examined the temporal and spatial pattern of expression of these genes using in situ hybrid ization. The uninduced metanephric blastema (MB) expressed abundant IG F-II mRNA. With induction by the ureteric duct (UD), the aggregated MB additionally expressed IGFBP-2 and IGFBP-4 mRNAs. The mature UD expre ssed IGFBP-3 mRNA while the ampulla in contact with the MB lacked IGFB P-3 mRNA and expressed IGFBP-2 exclusively. Upon formation of the S-sh ape nephron, IGFBP-2 mRNA was expressed in the committed glomerular an d epithelial cells which also expressed IGF-II and IGFBP-4, and the me senchyme of the vascular cleft expressed IGFBP-5 mRNA. In the maturing glomerulus, the glomerular epithelial cells expressed IGF-II mRNA tog ether with IGFBP-2 and IGFBP-4 mRNAs, while IGFBP-5 mRNA was localized to the mesangium and supporting mesenchyme. As the proximal tubule wa s formed the epithelium expressed less of IGFBP-2 mRNA and more of IGF BP-4 mRNA. The renal mesenchyme in the cortex and medulla expressed ab undant IGF-II mRNA, and lower levels of IGFBP-4 and -5 mRNAs. The epit helium of the collecting ducts and pelvicalyceal system expressed abun dant IGFBP-3. In contrast, IGF-I, IGFBP-1, and IGFBP-6 mRNAs were expr essed at low levels. The specific temporal and spatial pattern of expr ession of IGFBP genes on the background of abundant IGF-II gene expres sion suggests that the IGFBP peptides, as modulators of IGF action, ar e expressed locally at specific points of nephrogenesis to interact wi th IGF-II to regulate mesenchymal induction, renal epithelial cell com mit ment, differentiation and growth.