Perantoni A O, Dove L F, Karavanova I
Laboratory of Comparative Carcinogenesis, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702, USA.
Proc Natl Acad Sci U S A. 1995 May 9;92(10):4696-700. doi: 10.1073/pnas.92.10.4696.
The earliest characterized events during induction of tubulogenesis in renal anlage include the condensation or compaction of metanephrogenic mesenchyme with the concurrent upregulation of WT1, the gene encoding the Wilms tumor transcriptional activator/suppressor. We report that basic fibroblast growth factor (FGF2) can mimic the early effects of an inductor tissue by promoting the condensation of mesenchyme and inhibiting the tissue degeneration associated with the absence of an inductor tissue. By in situ hybridization, FGF2 was also found to mediate the transcriptional activation of WT1 and of the hepatocyte growth factor receptor gene, c-met. Although FGF2 can induce these early events of renal tubulogenesis, it cannot promote the epithelial conversion associated with tubule formation in metanephrogenic mesenchyme. For this, an undefined factor(s) from pituitary extract in combination with FGF2 can cause tubule formation in uninduced mesenchyme. These findings support the concept that induction in kidney is a multiphasic process that is mediated by more than a single comprehensive inductive factor and that soluble molecules can mimic these inductive activities in isolated uninduced metanephrogenic mesenchyme.
在肾原基诱导肾小管形成过程中，最早被明确的事件包括后肾间充质的凝聚或紧实，同时编码威尔姆斯瘤转录激活因子/抑制因子的WT1基因上调。我们报告称，碱性成纤维细胞生长因子（FGF2）可通过促进间充质凝聚并抑制与缺乏诱导组织相关的组织退化，来模拟诱导组织的早期作用。通过原位杂交还发现，FGF2可介导WT1以及肝细胞生长因子受体基因c-met的转录激活。尽管FGF2可诱导肾小管形成的这些早期事件，但它无法促进后肾间充质中与肾小管形成相关的上皮转化。为此，垂体提取物中一种未明确的因子与FGF2联合使用，可在未诱导的间充质中导致肾小管形成。这些发现支持了这样一种概念，即肾脏中的诱导是一个多阶段过程，由不止一种综合诱导因子介导，并且可溶性分子可在分离的未诱导后肾间充质中模拟这些诱导活性。
