Plisov S Y, Yoshino K, Dove L F, Higinbotham K G, Rubin J S, Perantoni A O
Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick, MD 21702, USA.
Development. 2001 Apr;128(7):1045-57. doi: 10.1242/dev.128.7.1045.
The metanephric kidney develops from interactions between the epithelial ureteric bud and adjacent metanephric mesenchyme, which is induced by the bud to form the epithelia of the nephron. We have found that leukemia inhibitory factor (LIF) and transforming growth factor beta 2 (TGF beta 2) are secreted by inductive rat bud cells and cooperate to enhance and accelerate renal tubule formation in uninduced rat metanephric mesenchymal explants. LIF alone or TGF beta 2 with fibroblast growth factor 2 induced numerous tubules in isolated mesenchymes over an 8 day period, while (in combination) all three caused abundant tubule formation in 72 hours. Furthermore, neutralization of Wnt ligands with antagonist-secreted Frizzled-related protein 1 abrogated these responses and combinatorial cytokine/growth factor stimulation of explants augmented nuclear activation of Tcf1/Lef1, suggesting that LIF and TGF beta 2/FGF2 cooperate to regulate nephrogenesis through a common Wnt-dependent mechanism.
后肾由上皮输尿管芽与相邻的后肾间充质相互作用发育而成，后肾间充质被芽诱导形成肾单位的上皮。我们发现白血病抑制因子（LIF）和转化生长因子β2（TGFβ2）由诱导性大鼠芽细胞分泌，并协同增强和加速未诱导的大鼠后肾间充质外植体中的肾小管形成。单独的LIF或TGFβ2与成纤维细胞生长因子2在8天时间内诱导分离的间充质中形成大量肾小管，而三者联合在72小时内导致大量肾小管形成。此外，用分泌拮抗剂的卷曲相关蛋白1中和Wnt配体消除了这些反应，外植体的组合细胞因子/生长因子刺激增强了Tcf1/Lef1的核激活，表明LIF和TGFβ2/FGF2通过共同的Wnt依赖机制协同调节肾发生。
