Müller Cell-Derived PEDF Mediates Neuroprotection via STAT3 Activation
| Autor: | Helena Savkovic-Cvijic, Peter Wiedemann, Michael Beck, Jan Darius Unterlauft, Susanne Bürger, Wolfram Eichler, Andreas Reichenbach, Manuela Schmidt |
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| Rok vydání: | 2017 |
| Předmět: |
Receptors
Neuropeptide STAT3 Transcription Factor 0301 basic medicine Programmed cell death Cell Survival Physiology Ependymoglial Cells Cell Retinal ganglion cells Neuroprotection Retinal ganglion lcsh:Physiology lcsh:Biochemistry Mice 03 medical and health sciences chemistry.chemical_compound PEDF medicine Animals lcsh:QD415-436 Nerve Growth Factors Phosphorylation RNA Small Interfering Eye Proteins STAT3 Serpins Müller cells lcsh:QP1-981 biology Interleukin-6 Retinal Lipase Cell Hypoxia Coculture Techniques Cyclic S-Oxides Rats Cell biology 030104 developmental biology medicine.anatomical_structure chemistry biology.protein RNA Interference sense organs Signal transduction Signal Transduction |
| Zdroj: | Cellular Physiology and Biochemistry, Vol 44, Iss 4, Pp 1411-1424 (2017) |
| ISSN: | 1421-9778 1015-8987 |
| DOI: | 10.1159/000485537 |
| Popis: | Background/ Aims: This study was performed to reveal signaling pathways exploited by pigment epithelium-derived factor (PEDF) derived from retinal (glial) Müller cells to protect retinal ganglion cells (RGCs) from cell death. Methods: The survival of RGCs was determined in the presence of conditioned culture media (MCM) from or in co-cultures with Müller cells. The significance of PEDF-induced STAT3 activation was evaluated in viability assays and using Western blotting analyses and siRNA-transfected cells. Results: Secreted mediators of Müller cells increased survival of RGCs under normoxia or hypoxia to a similar degree as of PEDF- or IL-6-exposed cells. PEDF and MCM induced an increased STAT3 activation in RGCs and R28 cells, and neutralization of PEDF in MCM attenuated STAT3 activation. Inhibition of STAT3 reduced PEDF-promoted survival of RGCs. Similar to IL-6, PEDF induced STAT3 activation, acting in a dose-dependent manner via the PEDF receptor (PEDF-R) encoded by the PNPLA2 gene. Ablation of PEDF-R attenuated MCM-induced STAT3 activation and compromised the viability of PEDF-exposed R28 cells. Conclusions: Müller cells are an important source of PEDF, which promotes RGC survival through STAT3 activation and, at least in part, via PEDF-R. Enhancing the secretory function of Müller cells may be useful to promote RGC survival in retinal neurodegenerative diseases. |
| Databáze: | OpenAIRE |
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