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Expression of leukemia inhibitory factor in Müller glia cells is regulated by a redox-dependent mRNA stability mechanism
- Source :
- BMC Biology
- Publication Year :
- 2015
-
Abstract
- Background Photoreceptor degeneration is a main hallmark of many blinding diseases making protection of photoreceptors crucial to prevent vision loss. Thus, regulation of endogenous neuroprotective factors may be key for cell survival and attenuation of disease progression. Important neuroprotective factors in the retina include H2O2 generated by injured photoreceptors, and leukemia inhibitory factor (LIF) expressed in Müller glia cells in response to photoreceptor damage. Results We present evidence that H2O2 connects to the LIF response by inducing stabilization of Lif transcripts in Müller cells. This process was independent of active gene transcription and p38 MAPK, but relied on AU-rich elements (AREs), which we identified within the highly conserved Lif 3′UTR. Affinity purification combined with quantitative mass spectrometry identified several proteins that bound to these AREs. Among those, interleukin enhancer binding factor 3 (ILF3) was confirmed to participate in the redox-dependent Lif mRNA stabilization. Additionally we show that KH-type splicing regulatory protein (KHSRP) was crucial for maintaining basal Lif expression levels in non-stressed Müller cells. Conclusions Our results suggest that H2O2-induced redox signaling increases Lif transcript levels through ILF3 mediated mRNA stabilization. Generation of H2O2 by injured photoreceptors may thus enhance stability of Lif mRNA and therefore augment neuroprotective LIF signaling during degenerative conditions in vivo. Electronic supplementary material The online version of this article (doi:10.1186/s12915-015-0137-1) contains supplementary material, which is available to authorized users.
- Subjects :
- Redox signaling
Physiology
RNA Stability
Plant Science
Leukemia Inhibitory Factor
1309 Developmental Biology
1307 Cell Biology
Mice
1315 Structural Biology
0302 clinical medicine
Structural Biology
1110 Plant Science
Müller glial cells
KHSRP
Regulation of gene expression
0303 health sciences
Agricultural and Biological Sciences(all)
Retinal Degeneration
MRNA stabilization
10174 Clinic for Gynecology
Neuroprotection
Cell biology
medicine.anatomical_structure
embryonic structures
1305 Biotechnology
Signal transduction
General Agricultural and Biological Sciences
Muller glia
Oxidation-Reduction
Biotechnology
Signal Transduction
Research Article
10018 Ophthalmology Clinic
endocrine system
Ependymoglial Cells
610 Medicine & health
1100 General Agricultural and Biological Sciences
Biology
p38 MAPK
General Biochemistry, Genetics and Molecular Biology
Retina
Cell Line
03 medical and health sciences
1300 General Biochemistry, Genetics and Molecular Biology
medicine
Animals
mRNA stability
Ecology, Evolution, Behavior and Systematics
030304 developmental biology
Messenger RNA
Biochemistry, Genetics and Molecular Biology(all)
LIF
1314 Physiology
Cell Biology
Hydrogen Peroxide
ILF3
Rats
1105 Ecology, Evolution, Behavior and Systematics
Gene Expression Regulation
Cell culture
sense organs
Leukemia inhibitory factor
030217 neurology & neurosurgery
Developmental Biology
Subjects
Details
- ISSN :
- 17417007
- Volume :
- 13
- Database :
- OpenAIRE
- Journal :
- BMC biology
- Accession number :
- edsair.doi.dedup.....1a2bcd333d72524a3bf86f0803462bbb