Basic Science Research

Presentation Title (IN ALL CAPS)

POST-TRANSCRIPTIONAL REGULATION OF ASTROCYTE-TISSUE INHIBITOR OF METALLOPROTEINASE-1 (TIMP-1) IN HAND

Departmental Affiliation and City, State, Zip for All Authors

3500 Camp Bowie Blvd, Fort Worth, TX 76107

Classification

GSBS Student (For Competition)

Research Presentation Category

Basic Science Research

Brief Narrative or Summary

In summary we can state that IL-1β activation significantly increased miRNA155 and miRNA146b levels in human astrocytes.miRNA155 and miRNA146b overexpression significantly reduced luciferase activity in reporter constructs controlled by TIMP-1 3’UTR and miRNA 155 and 146b also reduced endogenous TIMP-1 levels in IL-1β-activated astrocytes.Thus astrocyte TIMP-1 may be post-transcriptionally regulated by miR146b and miR155 during HAND.

Scientific Abstract

HIV-1 can lead to several central nervous system impairments together termed HIV-1-associated neurocognitive disorders (HAND). In acute versus chronic neuroinflammation, differential regulation of Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) is relevant to HAND neuropathogenesis. However, the underlying mechanisms are still being uncovered. In our study, we investigated the post-transcriptional regulation of TIMP-1 3’UTR via miRNAs. Microarray analysis was used to analyze miRNA changes in IL-1β-activated astrocytes. To investigate miRNA-mediated TIMP-1 3’UTR post-transcriptional regulation, TIMP-1 3’UTR and miRNA overexpression constructs were used. Primary human astrocytes were transfected with TIMP-1 3’UTR and miR146b or miR155 by nucleofection. Twenty-four hours post-transfection, astrocytes were treated with IL-1β. Firefly luciferase activity and TIMP-1 levels in astrocytes were monitored in parallel experiments after one and three days post-IL-1β treatment. Microarray analysis showed an increase in 12 miRNAs and decrease in 4 miRNAs. Seven of those were further confirmed by RT-PCR. The most increased were miRNA155 and miRNA146b. Overexpression of miRNA155 and miRNA146b in IL-1β-activated astrocytes decreased both luciferase activity and endogenous TIMP-1 levels.In summary, we can state that astrocyte-TIMP-1 may be regulated post-transcriptionally by miRNAs (146b and 155) during HAND.

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POST-TRANSCRIPTIONAL REGULATION OF ASTROCYTE-TISSUE INHIBITOR OF METALLOPROTEINASE-1 (TIMP-1) IN HAND

HIV-1 can lead to several central nervous system impairments together termed HIV-1-associated neurocognitive disorders (HAND). In acute versus chronic neuroinflammation, differential regulation of Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) is relevant to HAND neuropathogenesis. However, the underlying mechanisms are still being uncovered. In our study, we investigated the post-transcriptional regulation of TIMP-1 3’UTR via miRNAs. Microarray analysis was used to analyze miRNA changes in IL-1β-activated astrocytes. To investigate miRNA-mediated TIMP-1 3’UTR post-transcriptional regulation, TIMP-1 3’UTR and miRNA overexpression constructs were used. Primary human astrocytes were transfected with TIMP-1 3’UTR and miR146b or miR155 by nucleofection. Twenty-four hours post-transfection, astrocytes were treated with IL-1β. Firefly luciferase activity and TIMP-1 levels in astrocytes were monitored in parallel experiments after one and three days post-IL-1β treatment. Microarray analysis showed an increase in 12 miRNAs and decrease in 4 miRNAs. Seven of those were further confirmed by RT-PCR. The most increased were miRNA155 and miRNA146b. Overexpression of miRNA155 and miRNA146b in IL-1β-activated astrocytes decreased both luciferase activity and endogenous TIMP-1 levels.In summary, we can state that astrocyte-TIMP-1 may be regulated post-transcriptionally by miRNAs (146b and 155) during HAND.