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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Acute liver failure-induced hepatic encephalopathy is associated with changes in microRNA expression profiles in cerebral cortex of the rat

Texto completo
Autor(es):
Vemuganti, Raghu [1] ; Silva, Vinicius R. [2] ; Mehta, Suresh L. [1] ; Hazell, Alan S. [3, 2, 4]
Número total de Autores: 4
Afiliação do(s) autor(es):
[1] Univ Wisconsin, Dept Neurol Surg, Madison, WI - USA
[2] Univ Estadual Campinas UNICAMP, Dept Neurol, Campinas, SP - Brazil
[3] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7 - Canada
[4] CRCHUM, NeuroRescue Lab, Montreal, PQ H2X 0A9 - Canada
Número total de Afiliações: 4
Tipo de documento: Artigo Científico
Fonte: METABOLIC BRAIN DISEASE; v. 29, n. 4, SI, p. 891-899, DEC 2014.
Citações Web of Science: 7
Resumo

The mechanisms that promote brain dysfunction after acute liver failure (ALF) are not clearly understood. The small noncoding RNAs known as microRNAs (miRNAs) significantly control mRNA translation and thus normal and pathological functions in the mammalian body. To understand their significance in ALF, we currently profiled the expression of miRNAs in the cerebral cortex of mice sacrificed at coma stage following treatment with azoxymethane. Of the 470 miRNAs profiled using microarrays, 37 were significantly altered (20 up-and 17 down-regulated) in their expression in the ALF group compared to sham group. In silico analysis showed that the ALF-responsive miRNAs target on average 231 mRNAs/miRNA (range: 3 to 840 targets). Pathways analysis showed that many miRNAs altered after ALF target multiple mRNAs that are part of various biological and molecular pathways. Glutamatergic synapse, Wnt signaling, MAP-kinase signaling, axon guidance, PI3-kinase-AKT signaling, T-cell receptor signaling and ubiquitin-mediated proteolysis are the top pathways targeted by the ALF-sensitive miRNAs. At least 28 ALF-responsive miRNAs target each of the above pathways. We hypothesize that alterations in miRNAs and their down-stream mRNAs of signaling pathways might play a role in the induction and progression of neurological dysfunction observed during ALF. (AU)

Processo FAPESP: 11/02263-3 - Fisiopatologia da disfunção do transporte cerebral de glutamato na insuficiência hepática aguda
Beneficiário:Alan Stewart Hazell
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 12/15660-3 - Papel da neurotransmição glutamatérgica na insuficiência hepática aguda (ALF).
Beneficiário:Vinícius Rodrigues Silva
Linha de fomento: Bolsas no Brasil - Doutorado