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Expression of leukemia inhibitory factor in Müller glia cells is regulated by a redox-dependent mRNA stability mechanism

Overview of attention for article published in BMC Biology, April 2015
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Title
Expression of leukemia inhibitory factor in Müller glia cells is regulated by a redox-dependent mRNA stability mechanism
Published in
BMC Biology, April 2015
DOI 10.1186/s12915-015-0137-1
Pubmed ID
Authors

Cavit Agca, Karsten Boldt, Andrea Gubler, Isabelle Meneau, Armelle Corpet, Marijana Samardzija, Manuel Stucki, Marius Ueffing, Christian Grimm

Abstract

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. 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. Our results suggests 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.

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The data shown below were compiled from readership statistics for 24 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 24 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 6 25%
Student > Master 4 17%
Lecturer 2 8%
Other 2 8%
Professor 2 8%
Other 4 17%
Unknown 4 17%
Readers by discipline Count As %
Neuroscience 6 25%
Agricultural and Biological Sciences 5 21%
Biochemistry, Genetics and Molecular Biology 4 17%
Pharmacology, Toxicology and Pharmaceutical Science 1 4%
Immunology and Microbiology 1 4%
Other 3 13%
Unknown 4 17%