TY - JOUR
T1 - Species-specific microRNA roles elucidated following astrocyte activation
AU - Mor, Eyal
AU - Cabilly, Yuval
AU - Goldshmit, Yona
AU - Zalts, Harel
AU - Modai, Shira
AU - Edry, Liat
AU - Elroy-Stein, Orna
AU - Shomron, Noam
N1 - Funding Information: Chief Scientist Office, Ministry of Health, Israel (grant No. 3-4876); the Kunz-Lion Foundation; the Ori Levi Foundation for Mitochondrial Research; the Schreiber foundation of Tel Aviv University’s Faculty of Medicine; the Wolfson family Charitable Fund; the Legacy Heritage Biomedical Science Partnership Program of the Israel Science Foundation (grant No. 1911/08). Funding Information: The authors thank Prof. Marcello Rosa (Monash University) for providing brain tissue, collected as part of experiments funded by NHMRC project grant 491022 ‘Plasticity of the primate cerebral cortex’. The authors also thank Prof. Reuven Stein, Lior Mayo and Jakob Rukov for commenting on the article. E.M., Y.C., Y.G., O.E.-S., and N.S. designed research; E.M., Y.C., Y.G., H.Z., S.M., and L.E. performed research; E.M., Y.C., H.Z., O.E.-S., and N.S analyzed data; E.M., O.E.-S., and N.S. wrote the article. This work was performed in partial fulfillment of the requirements for a Ph.D. degree of E.M, Sackler Faculty of Medicine, Tel Aviv University.
PY - 2011/5
Y1 - 2011/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79956014029&partnerID=8YFLogxK
U2 - https://doi.org/10.1093/nar/gkq1325
DO - https://doi.org/10.1093/nar/gkq1325
M3 - مقالة
C2 - 21247879
SN - 0305-1048
VL - 39
SP - 3710
EP - 3723
JO - Nucleic acids research
JF - Nucleic acids research
IS - 9
ER -
