Synergism between temporally distinct growth factors: bFGF, insulin and lens cell differentiation

• Published in: Mechanisms of development Vol. 67; no. 2; pp. 193 - 201
• Main Authors: Leenders, W.P.J., van Genesen, S.T., Schoenmakers, J.G.G., van Zoelen, E.J.J., Lubsen, N.H.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.10.1997
• Subjects: Animals; bFGF; Cell Differentiation - drug effects; Cells, Cultured; Differentiation; Fibroblast Growth Factor 2 - metabolism; Insulin; Insulin - metabolism; Lens; Lens, Crystalline - cytology; Lens, Crystalline - metabolism; Phenotype; Protein Kinase C - antagonists & inhibitors; Protein Kinase C - metabolism; Rats; Rats, Wistar; Tetradecanoylphorbol Acetate - pharmacology; TPA; Lens; TPA; Differentiation; Insulin; bFGF
• ISSN: 0925-4773; 1872-6356
• DOI: 10.1016/S0925-4773(97)00121-4

Fibroblast growth factors (FGFs) are the only known factors that can induce differentiation of the mammalian lens epithelial cell, while insulin acts only as a mitogen, not as a morphogen. We show here that insulin enhances expression of the αA-crystallin gene in lens epithelial cells and induces the synthesis of lens fibre cell specific βB2- and γ-crystallins in early differentiated fibre cells. Different signal transduction pathways are required for bFGF or insulin maintained fibre cell differentiation. A 15 min preincubation with bFGF was sufficient for the lens epithelial cells to become competent to undergo insulin maintained differentiation. The phorbol ester TPA could replace bFGF. The bFGF instructed competence to differentiate decays with a half-life of about 30 h. Hence, bFGF and insulin can act in concert to produce a differentiated phenotype even when they are not present simultaneously.