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E-GEOD-66278 - Taqman miRNA Array on Murine livers with varying amounts of carbon tetrachloride induced liver fibrosis

Status
Released on 25 February 2015, last updated on 27 February 2015
Organism
Mus musculus
Samples (8)
Array (1)
Protocols (7)
Description
Abstract from Knabel et al. PLoS One (2015): Fibrosis refers to the accumulation of excess extracellular matrix (ECM) components and represents a key feature of many chronic inflammatory diseases. Unfortunately, no currently available treatments specifically target this important pathogenic mechanism. MicroRNAs (miRNAs) are short, non-coding RNAs that post-transcriptionally repress target gene expression and the development of miRNA-based therapeutics is being actively pursued for a diverse array of diseases. Because a single miRNA can target multiple genes, often within the same pathway, variations in the level of individual miRNAs can potently influence disease phenotypes. Members of the miR-29 family, which include mir29a, miR-29b and miR-29c, are strong inhibitors of ECM synthesis and fibrosis-associated decreases in miR-29 have been reported in multiple organs. We observed downregulation of miR-29a/b/c in fibrotic livers of carbon tetrachloride (CCl4) treated mice as well as in isolated human hepatocytes exposed to the pro-fibrotic cytokine TGF-β. Importantly, we demonstrate that a single systemic injection of a miR-29a expressing adeno-associated virus (AAV) can prevent and even reverse histologic and biochemical evidence of fibrosis despite continued exposure to CCl4. The observed therapeutic benefits were associated with AAV transduction of hepatocytes but not hepatic stellate cells, which are the main ECM producing cells in fibroproliferative liver diseases. Our data therefore demonstrate that delivery of mir-29 to the hepatic parenchyma using a clinically relevant gene delivery platform protects injured livers against fibrosis and, given the consistent fibrosis-associated downregulation of miR-29, suggests AAV-miR-29 based therapies may be effective in treating a variety of fibroproliferative disorders. The Taqman MicroRNA Array (Taqman Array Rodent MicroRNA A Cards v2.0, ABI) was run, using manufacturer's protocols, on 3 groups of mice with varying amounts fibrotic injury. The groups include carbon tetrachloride intraperitinially injected bi-weekly for 1, 4, and 8 weeks with n=4, 3, and 2 respectively for each group. The RNA was isolated from whole liver using the MiRvana miRNA Isolation Kit (Ambion) according to manufacturer's protocols. The fold_change.txt contains the following data columns; ID_Ref: mmu-miR being quantified not-treated (FC): Fold Change compared to not-treated group using Geometric mean normalization 1 week (FC): Fold Change compared to not-treated group using Geometric mean normalization 4 weeks (FC): Fold Change compared to not-treated group using Geometric mean normalization 8 weeks (FC): Fold Change compared to not-treated group using Geometric mean normalization
Experiment type
other 
Contacts
Tyler J Creamer <tcreamer@jhmi.edu>, Andrew M Cameron, Daniel S Warren, Farooq Sheikh, Hun-Way Hwang, Joshua T Mendell, K R Clark, Kalyani Ramachandran, Matthew K Knabel, Michael Torbenson, Raghu R Chivukula, Robert A Montgomery, Sunil Karhadkar
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-66278.idf.txt
Sample and data relationshipE-GEOD-66278.sdrf.txt
Processed data (1)E-GEOD-66278.processed.1.zip
Additional data (1)E-GEOD-66278.additional.1.zip
Array designA-GEOD-17017.adf.txt
Links