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Unique microRNA Expression in the Colonic Mucosa During Chronic HIV-1 Infection.

AIDS; 2017 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-28692540

Resumo

OBJECTIVE: Chronic HIV-1 infection leads to widespread inflammation and immune dysregulation. The gastrointestinal mucosa, a primary site for HIV-1 replication, is thought to play a significant role in this response. MicroRNAs (miRs) are small non-coding RNAs that regulate gene expression, including immune activation and inflammation. Here we investigate miR expression and function in the colonic mucosa during HIV-1 infection. DESIGN AND METHODS: Using miR profiling, we examined miR expression in the colonic mucosa of HIV-infected subjects. These miRs were further parsed to identify those that most likely function in HIV-related inflammation. Using bioinformatics tools, we identified potential target genes which were confirmed using in vitro functional testing. RESULTS: We identified twelve miRs that were differentially expressed in the colonic mucosa of HIV-infected subjects with high versus undetectable plasma viral concentrations. Of these, both miR-26a and miR-29a were down-regulated in untreated HIV-1 infection, yet not in the colonic mucosa from inflammatory bowel disease. This down-regulation occurs within the first hours after infection. These miRs were further shown to directly target IL-6 and STAT3, respectively, with similar changes confirmed in an ex vivo explant infection model. CONCLUSIONS: miR-26a and miR-29a levels are decreased in the colonic mucosa during chronic HIV-1 infection, and this change may be initiated during acute infection. Both miRs de-repress the IL-6/STAT3 signaling pathway, which could contribute to increased inflammation during infection. These miRs may represent novel therapeutic targets for HIV-1 associated inflammation in the colonic mucosa.