Expression and localization of fibroblast growth factors and fibroblast growth factor receptors in the developing rat kidney
Expression and localization of fibroblast growth factors and fibroblast growth factor receptors in the developing rat kidney
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DOI：
10.1046/j.1523-1755.1999.00781.x
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发表时间：
1999-12-01
影响因子：
19.6
通讯作者：
Bertram, JF
中科院分区：
文献类型：
--
作者：
Cancilla, B;Ford-Perriss, MD;Bertram, JF
背景。永久肾，或后肾，通过一系列复杂的相互诱导事件发展，包括分支形态发生、小管发生、血管生成和组织重塑。成纤维细胞生长因子（FGFs）是一个与后肾发育有关的生长和分化因子家族。FGFR通过四个FGFR基因（FGFR1至FGFR4）编码的酪氨酸激酶受体（FGFR）发挥作用。采用逆转录聚合酶链反应检测胚胎14 ~ 21日大鼠后肾中FGFs和fgfr的表达。采用非放射性原位杂交法定位E20大鼠后肾中FGF1 mRNA，采用免疫组化法定位E15和E20大鼠后肾中的fgfr。我们检测了从E14到E21大鼠后肾酚中FGF1 - FGF5、FGF7 - FGF10和FGFR1 - FGFR4 （IIIb和IIIc剪接变体）mrna的表达。通过原位杂交，在肾原区、输尿管上皮和发育中的肾元元件中检测到FGF1 mRNA。FGFR蛋白以一种独特的模式定位，随着成熟而改变。FGFR1广泛分布于发育中的后肾上皮和间质，但不分布于发育中的间质。FGFR2也广泛分布于肾细胞上皮，尤其是近曲小管，但未在后肾间质、间质凝聚物或发育间质中检测到。FGFR3定位于间质凝聚物、肾元元件和髓质间质，但未发现近曲小管；FGFR4主要定位于成熟肾元结构，未在肾原间质、间质凝聚物或发育间质中检测到。这些结果表明，FGFs和fgfr至少从E14开始就在发育中的大鼠后肾中表达，并且它们可能在后肾的发育和成熟中发挥重要作用。
Background. The permanent kidney, or metanephros, develops through a complex series of reciprocal inductive events and involves branching morphogenesis, tubulogenesis, angiogenesis, and tissue remodeling. Fibroblast growth factors (FGFs) are a family of growth and differentiation factors that have been implicated in metanephric development. FGFs exert their actions through tyrosine kinase receptors, FGFRs, which are encoded by four FGFR genes (FGFR1 through FGFR4).Methods. Reverse transcriptase-polymerase chain reaction was used to detect the expression of FGFs and FGFRs in rat metanephroi from embryonic day (E) 14 to E21. Nonradioactive in situ hybridization was used to localize FGF1 mRNA in E20 rat metanephroi, and immunohistochemistry was used to localize FGFRs in E15 and E20 rat metanephroi.Results. We detected the expression of mRNAs for FGF1 through FGF5, FGF7 through FGF10, and FGFR1 through FGFR4 (IIIb and IIIc splice variants) in rat metanephrol from E14 to E21. By in situ hybridization, FGF1 mRNA was detected in the nephrogenic zone, ureteric epithelium, and developing nephron elements. FGFR proteins were localized in a distinct pattern that altered with maturation. FGFR1 was widely distributed in developing metanephric epithelia and mesenchyme, but not in developing interstitium. FGFR2 was also widely distributed in nephron epithelia, particularly in proximal convoluted tubules, but was not detected in metanephric mesenchyme, mesenchymal condensates, or developing interstitium. FGFR3 was localized to mesenchymal condensates, nephron elements, and medullary interstitium but not proximal convoluted tubules, FGFR4 was localized mostly to maturing nephron structures and was not detected in nephrogenic mesenchyme, mesenchymal condensates, or developing interstitium.Conclusions. These results indicate that FGFs and FGFRs are expressed in the developing rat metanephros from at least E14 and that they likely play important roles in metanephric development and maturation.