TGF-β signaling is required for maintenance of retinal ganglion cell differentiation and survival
| Autor: | Tony E. Walshe, Lyndsay L. Leach, Patricia A. D'Amore |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Retinal Ganglion Cells
MAPK/ERK pathway Neurite Cell Survival MAP Kinase Signaling System Cellular differentiation Intracellular Space Apoptosis Smad Proteins Biology Article Cell Line Transforming Growth Factor beta1 chemistry.chemical_compound Neurites medicine Animals Humans Cilia Propidium iodide Retina General Neuroscience Cell Differentiation Epithelial Cells Rats Cell biology medicine.anatomical_structure chemistry Retinal ganglion cell Cell culture Culture Media Conditioned sense organs Signal transduction Biomarkers Signal Transduction |
| Zdroj: | Neuroscience. 189:123-131 |
| ISSN: | 0306-4522 |
| DOI: | 10.1016/j.neuroscience.2011.05.020 |
| Popis: | Purpose. To determine the role of TGF-β1 in the maintenance of retinal ganglion cell line (RGC-5) differentiation and integrity. Methods. RGC-5 cells were differentiated in media conditioned by human non-pigmented ciliary epithelial cells (HNPE) for 4 days before treatment with TGF-β1 for 24 h. Cells were examined for morphological changes and harvested for western blot and real-time PCR analysis. For study of apoptosis, differentiated RGC-5 cells were grown in serum-free medium for 24 h in the presence or absence of TGF-β1 and collected for Annexin V/Propidium iodide FACs analysis. The role of MAPK pathways in TGF-β1-dependent signaling was determined by treatment with specific inhibitors of ERK, JNK and p38. Results. Differentiation of RGC-5 cells in HNPE-conditioned media (CM) increased the neural cell markers, Brn-3c, NF-160, Thy1.2, Tau and PGP9.5. Treatment with TGF-β1 significantly increased the length of neurites extended by differentiated RGC-5s, concomitant with increased expression of NF-160 and PGP9.5, but not Brn-3c, Thy1.2 or Tau. TGF-β1 also decreased RGC-5 cell apoptosis in serum-free medium. p38 phosphorylation, but not smad2/3, JNK or ERK phosphorylation, was increased in TGF-β1 treated cells. Specific inhibition of p38 signaling reversed TGF-β1 induced neurite growth. Conclusions. These findings demonstrate the induction of RGC-5 cell differentiation by HNPE-derived CM and illustrate a role for TGF-β1 in maintaining RGC-5 cell survival and promoting neurite outgrowth through p38 MAPK. |
| Databáze: | OpenAIRE |
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