Müller Cell-Derived PEDF Mediates Neuroprotection via STAT3 Activation.

Publisher: Cell Physiol Biochem Press GmbH & Co KG Country of Publication: Germany NLM ID: 9113221 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1421-9778 (Electronic) Linking ISSN: 10158987 NLM ISO Abbreviation: Cell Physiol Biochem Subsets: MEDLINE

Publication: 2019- : Düsseldorf, Germany : Cell Physiol Biochem Press GmbH & Co KG
Original Publication: Basel ; New York : S. Karger, 1991-2018.

Ependymoglial Cells/*metabolism ; Eye Proteins/*metabolism ; Nerve Growth Factors/*metabolism ; STAT3 Transcription Factor/*metabolism ; Serpins/*metabolism; Animals ; Cell Hypoxia ; Cell Survival/drug effects ; Coculture Techniques ; Cyclic S-Oxides/pharmacology ; Ependymoglial Cells/cytology ; Eye Proteins/antagonists & inhibitors ; Eye Proteins/genetics ; Eye Proteins/pharmacology ; Interleukin-6/pharmacology ; Lipase/antagonists & inhibitors ; Lipase/genetics ; Lipase/metabolism ; Mice ; Nerve Growth Factors/antagonists & inhibitors ; Nerve Growth Factors/genetics ; Nerve Growth Factors/pharmacology ; Phosphorylation/drug effects ; RNA Interference ; RNA, Small Interfering/metabolism ; Rats ; Receptors, Neuropeptide/metabolism ; Retinal Ganglion Cells/metabolism ; STAT3 Transcription Factor/antagonists & inhibitors ; Serpins/genetics ; Serpins/pharmacology ; Signal Transduction/drug effects

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.
(© 2017 The Author(s). Published by S. Karger AG, Basel.)

Keywords: Müller cells; Neuroprotection; PEDF; Retinal ganglion cells

0 (Cyclic S-Oxides)
0 (Eye Proteins)
0 (Interleukin-6)
0 (Nerve Growth Factors)
0 (RNA, Small Interfering)
0 (Receptors, Neuropeptide)
0 (STAT3 Transcription Factor)
0 (Serpins)
0 (pigment epithelium-derived factor)
0 (pigment epithelium-derived factor receptor)
0 (stattic)
EC 3.1.1.3 (Lipase)

Date Created: 20171130 Date Completed: 20180118 Latest Revision: 20190212

20231215

10.1159/000485537

29186716