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TGF beta 2, LIF and FGF2 cooperate to induce nephrogenesis

  1. Author:
    Plisov, S. Y.
    Yoshino, K.
    Dove, L. F.
    Higinbotham, K. G.
    Rubin, J. S.
    Perantoni, A. O.

  2. Author Address

    NCI, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. NCI, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA. Perantoni AO NCI, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA.
    1. Year: 2001
  2. Journal: Development
    1. 128
    2. 7
    3. Pages: 1045-1057
  4. Type of Article: Article
  1. Abstract:

    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 beta2 (TGF beta2) 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 beta2 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 beta2/FGF2 cooperate to regulate nephrogenesis through a common Wnt-dependent mechanism.

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