TGF beta 2, LIF and FGF2 cooperate to induce nephrogenesis.
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.
Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick, MD 21702, USA.
S Y
SY
Plisov
K
K
Yoshino
L F
LF
Dove
K G
KG
Higinbotham
J S
JS
Rubin
A O
AO
Perantoni
D030201:Activin Receptors, Type I; D000818:Animals; D015415:Biomarkers; D017077:Culture Media, Conditioned; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism*; D006131:Growth Inhibitors / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008024:Ligands; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism*; D009399:Nephrons / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051381:Rats; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018121:Receptors, Cytokine / Q000235:genetics; D053606:Receptors, OSM-LIF; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D053781:Transforming Growth Factor beta2; D051153:Wnt Proteins; D060528:Wnt4 Protein
D015415:Biomarkers; D017077:Culture Media, Conditioned; D006131:Growth Inhibitors; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; C507842:Lifr protein, rat; D008024:Ligands; D008222:Lymphokines; D011518:Proto-Oncogene Proteins; D018121:Receptors, Cytokine; D053606:Receptors, OSM-LIF; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2; D051153:Wnt Proteins; D060528:Wnt4 Protein; C555583:Wnt4 protein, rat; D016222:Fibroblast Growth Factor 2; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; C000625843:Tgfbr1 protein, rat