Species-specific microRNA roles elucidated following astrocyte activation.
MicroRNAs (miRNAs) are short non-coding RNAs that play a central role in regulation of gene expression by binding to target genes. Many miRNAs were associated with the function of the central nervous system (CNS) in health and disease. Astrocytes are the CNS most abundant glia cells, providing support by maintaining homeostasis and by regulating neuronal signaling, survival and synaptic plasticity. Astrocytes play a key role in repair of brain insults, as part of local immune reactivity triggered by inflammatory or pathological conditions. Thus, astrocyte activation, or astrogliosis, is an important outcome of the innate immune response, which can be elicited by endotoxins such as lipopolysaccharide (LPS) and cytokines such as interferon-gamma (IFN-γ). The involvement of miRNAs in inflammation and stress led us to hypothesize that astrogliosis is mediated by miRNA function. In this study, we compared the miRNA regulatory layer expressed in primary cultured astrocyte derived from rodents (mice) and primates (marmosets) brains upon exposure to LPS and IFN-γ. We identified subsets of differentially expressed miRNAs some of which are shared with other immunological related systems while others, surprisingly, are mouse and rat specific. Of interest, these specific miRNAs regulate genes involved in the tumor necrosis factor-alpha (TNF-α) signaling pathway, indicating a miRNA-based species-specific regulation. Our data suggests that miRNA function is more significant in the mechanisms governing astrocyte activation in rodents compared to primates.
Department of Cell and Developmental Biology, Sackler Faculty of Medicine, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
Eyal
E
Mor
Yuval
Y
Cabilly
Yona
Y
Goldshmit
Harel
H
Zalts
Shira
S
Modai
Liat
L
Edry
Orna
O
Elroy-Stein
Noam
N
Shomron
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001483:Base Sequence; D002144:Callithrix; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D008969:Molecular Sequence Data; D051381:Rats; D015398:Signal Transduction; D013045:Species Specificity; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D035683:MicroRNAs; D014409:Tumor Necrosis Factor-alpha
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