Matsell D G, Delhanty P J, Stepaniuk O, Goodyear C, Han V K
Department of Pediatrics, University of Western Ontario, London, Canada.
Kidney Int. 1994 Oct;46(4):1031-42. doi: 10.1038/ki.1994.364.
To study the role of insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) in human nephrogenesis, we examined the temporal and spatial pattern of expression of these genes using in situ hybridization. The uninduced metanephric blastema (MB) expressed abundant IGF-II mRNA. With induction by the ureteric duct (UD), the aggregated MB additionally expressed IGFBP-2 and IGFBP-4 mRNAs. The mature UD expressed IGFBP-3 mRNA while the ampulla in contact with the MB lacked IGFBP-3 mRNA and expressed IGFBP-2 exclusively. Upon formation of the S-shape nephron, IGFBP-2 mRNA was expressed in the committed glomerular and epithelial cells which also expressed IGF-II and IGFBP-4, and the mesenchyme of the vascular cleft expressed IGFBP-5 mRNA. In the maturing glomerulus, the glomerular epithelial cells expressed IGF-II mRNA together with IGFBP-2 and IGFBP-4 mRNAs, while IGFBP-5 mRNA was localized to the mesangium and supporting mesenchyme. As the proximal tubule was formed the epithelium expressed less of IGFBP-2 mRNA and more of IGFBP-4 mRNA. The renal mesenchyme in the cortex and medulla expressed abundant IGF-II mRNA, and lower levels of IGFBP-4 and -5 mRNAs. The epithelium of the collecting ducts and pelvicalyceal system expressed abundant IGFBP-3. In contrast, IGF-I, IGFBP-1, and IGFBP-6 mRNAs were expressed at low levels. The specific temporal and spatial pattern of expression of IGFBP genes on the background of abundant IGF-II gene expression suggests that the IGFBP peptides, as modulators of IGF action, are expressed locally at specific points of nephrogenesis to interact with IGF-II to regulate mesenchymal induction, renal epithelial cell commitment, differentiation and growth.
为研究胰岛素样生长因子（IGFs）及其结合蛋白（IGFBPs）在人类肾发生中的作用，我们采用原位杂交技术检测了这些基因的表达时空模式。未诱导的后肾胚基（MB）表达丰富的IGF-II mRNA。在输尿管芽（UD）诱导下，聚集的MB额外表达IGFBP-2和IGFBP-4 mRNA。成熟的UD表达IGFBP-3 mRNA，而与MB接触的壶腹部缺乏IGFBP-3 mRNA，仅表达IGFBP-2。在S形肾单位形成时，IGFBP-2 mRNA在已定向的肾小球和上皮细胞中表达，这些细胞也表达IGF-II和IGFBP-4，血管裂隙的间充质表达IGFBP-5 mRNA。在成熟的肾小球中，肾小球上皮细胞同时表达IGF-II mRNA以及IGFBP-2和IGFBP-4 mRNA，而IGFBP-5 mRNA定位于系膜和支持性间充质。随着近端小管的形成，上皮细胞表达的IGFBP-2 mRNA减少，而IGFBP-4 mRNA增多。皮质和髓质的肾间充质表达丰富的IGF-II mRNA，以及较低水平的IGFBP-4和-5 mRNA。集合管和肾盂系统的上皮细胞表达丰富的IGFBP-3。相比之下，IGF-I、IGFBP-1和IGFBP-6 mRNA表达水平较低。在丰富的IGF-II基因表达背景下，IGFBP基因特定的表达时空模式表明，作为IGF作用调节剂的IGFBP肽在肾发生的特定部位局部表达，与IGF-II相互作用，调节间充质诱导、肾上皮细胞定向、分化和生长。
