Regulation of Lens Gap Junctions by Transforming Growth Factor Beta
| Autor: | Linda S. Musil, Judy K. VanSlyke, Bruce A. Boswell |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Cell signaling
Embryo Nonmammalian Connexin Cell Communication Chick Embryo Fibroblast growth factor Gap junction assembly Connexins Transforming Growth Factor beta1 03 medical and health sciences 0302 clinical medicine Transforming Growth Factor beta Lens Crystalline medicine Animals Cell Interactions Molecular Biology 030304 developmental biology 0303 health sciences biology Gap junction Gap Junctions Epithelial Cells Articles Cell Biology Transforming growth factor beta Up-Regulation Cell biology Fibroblast Growth Factors medicine.anatomical_structure Lens (anatomy) 030221 ophthalmology & optometry biology.protein Signal transduction Signal Transduction |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 1059-1524 |
| Popis: | Using cultured lens epithelial cells, we discovered a new type of cross-talk between the FGF and TGF-β pathways, as well as a novel role for TGF-β and p38 kinase in the regulation of gap junctional intercellular communication. Our findings provide an explanation for how pathologically increased TGF-β signaling could contribute to cataract formation. Gap junction–mediated intercellular communication (GJIC) is essential for the proper function of many organs, including the lens. GJIC in lens epithelial cells is increased by FGF in a concentration-dependent process that has been linked to the intralenticular gradient of GJIC required for lens transparency. Unlike FGF, elevated levels of TGF-β are associated with lens dysfunction. We show that TGF–β1 or -2 up-regulates dye coupling in serum-free primary cultures of chick lens epithelial cells (dissociated cell-derived monolayer cultures [DCDMLs]) via a mechanism distinct from that utilized by other growth factors. Remarkably, the ability of TGF-β and of FGF to up-regulate GJIC is abolished if DCDMLs are simultaneously exposed to both factors despite undiminished cell–cell contact. This reduction in dye coupling is attributable to an inhibition of gap junction assembly. Connexin 45.6, 43, and 56–containing gap junctions are restored, and intercellular dye coupling is increased, if the activity of p38 kinase is blocked. Our data reveal a new type of cross-talk between the FGF and TGF-β pathways, as well as a novel role for TGF-β and p38 kinase in the regulation of GJIC. They also provide an explanation for how pathologically increased TGF-β signaling could contribute to cataract formation. |
| Databáze: | OpenAIRE |
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