Micro RNA-125b (miRNA-125b) function in astrogliosis and glial cell proliferation

Micro RNAs (miRNAs) are post-transcriptional modulators of gene expression that regulate the stability and translation of their target messenger RNAs (mRNAs). Here we report that the levels of a human brain-enriched miRNA-125b are up-regulated in interleukin-6 (IL-6)-stressed normal human astrocytes...

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Bibliographic Details
Published in:Neuroscience letters 2010-05, Vol.476 (1), p.18-22
Main Authors: Pogue, A.I., Cui, J.G., Li, Y.Y., Zhao, Y., Culicchia, F., Lukiw, W.J.
Format: Article
Language:English
Subjects:
Actins - metabolism
Alzheimer's disease (AD)
Astrocytes - cytology
Astrocytes - drug effects
Astrocytes - metabolism
Astrogliosis
Biological and medical sciences
CDKN2A
Cell Proliferation
Cell-cycle
Cells, Cultured
Cyclin-Dependent Kinase Inhibitor p16 - metabolism
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Down's syndrome (DS)
Fundamental and applied biological sciences. Psychology
GFAP
Glial Fibrillary Acidic Protein - metabolism
Humans
IL-6
Interleukin-6 - pharmacology
Medical sciences
MicroRNAs - biosynthesis
MicroRNAs - pharmacology
miRNA-125b
Neurology
Up-Regulation
Vertebrates: nervous system and sense organs
Vimentin
Vimentin - metabolism
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Summary:Micro RNAs (miRNAs) are post-transcriptional modulators of gene expression that regulate the stability and translation of their target messenger RNAs (mRNAs). Here we report that the levels of a human brain-enriched miRNA-125b are up-regulated in interleukin-6 (IL-6)-stressed normal human astrocytes (NHA), a treatment known to induce astrogliosis. In vitro, anti-miRNA-125b added exogenously to IL-6-stressed NHA cultures attenuated both glial cell proliferation and increased the expression of the cyclin-dependent kinase inhibitor 2A (CDKN2A), a miRNA-125b target and negative regulator of cell growth. A strong positive correlation between miRNA-125b abundance and the glial cell markers glial fibrillary acidic protein (GFAP) and vimentin, and CDKN2A down-regulation was noted in advanced Alzheimer's disease (AD) and in Down's syndrome (DS) brain, chronic neurological disorders associated with astrogliosis. The results suggest that miRNA-125b up-regulation contributes to astrogliosis and to defects in the cell cycle that are characteristic of degenerating brain tissues.
ISSN:0304-3940
1872-7972
DOI:10.1016/j.neulet.2010.03.054