Systemic Delivery of scAAV8-Encoded MiR-29a Ameliorates Hepatic Fibrosis in Carbon Tetrachloride-Treated Mice. (Record no. 1742)

MARC details
000 -LEADER
fixed length control field 04196nam a22006137a 4500
008 - FIXED-LENGTH DATA ELEMENTS--GENERAL INFORMATION
fixed length control field 160219s20152015 xxu||||| |||| 00| 0 eng d
022 ## - INTERNATIONAL STANDARD SERIAL NUMBER
International Standard Serial Number 1932-6203
040 ## - CATALOGING SOURCE
Original cataloging agency Ovid MEDLINE(R)
099 ## - LOCAL FREE-TEXT CALL NUMBER (OCLC)
PMID 25923107
245 ## - TITLE STATEMENT
Title Systemic Delivery of scAAV8-Encoded MiR-29a Ameliorates Hepatic Fibrosis in Carbon Tetrachloride-Treated Mice.
251 ## - Source
Source PLoS ONE [Electronic Resource]. 10(4):e0124411, 2015.
252 ## - Abbreviated Source
Abbreviated source PLoS ONE. 10(4):e0124411, 2015.
253 ## - Journal Name
Journal name PloS one
260 ## - PUBLICATION, DISTRIBUTION, ETC.
Year 2015
260 ## - PUBLICATION, DISTRIBUTION, ETC.
Manufacturer FY2016
266 ## - Date added to catalog
Date added to catalog 2016-05-24
501 ## - WITH NOTE
Local holdings Available online through MWHC library: 2006 - present
520 ## - SUMMARY, ETC.
Abstract 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 miR-29a, 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-beta. 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.
546 ## - LANGUAGE NOTE
Language note English
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element *Dependovirus/ge [Genetics]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element *Drug-Induced Liver Injury/th [Therapy]
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Topical term or geographic name entry element *Genetic Vectors/ad [Administration & Dosage]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element *Hepatocytes/me [Metabolism]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element *Liver Cirrhosis/th [Therapy]
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Topical term or geographic name entry element *MicroRNAs/ge [Genetics]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Animals
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Carbon Tetrachloride
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Topical term or geographic name entry element Cell Line
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Topical term or geographic name entry element Drug-Induced Liver Injury/ge [Genetics]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Drug-Induced Liver Injury/pa [Pathology]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Extracellular Matrix/me [Metabolism]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Extracellular Matrix/pa [Pathology]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Gene Expression Regulation
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Genetic Vectors/me [Metabolism]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Hepatic Stellate Cells/me [Metabolism]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Hepatic Stellate Cells/pa [Pathology]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Hepatocytes/pa [Pathology]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Humans
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Liver Cirrhosis/ci [Chemically Induced]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Liver Cirrhosis/ge [Genetics]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Liver Cirrhosis/pa [Pathology]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Mice
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element MicroRNAs/me [Metabolism]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Transforming Growth Factor beta/ai [Antagonists & Inhibitors]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Transforming Growth Factor beta/pd [Pharmacology]
651 ## - SUBJECT ADDED ENTRY--GEOGRAPHIC NAME
Institution MedStar Heart & Vascular Institute
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Medline publication type Journal Article
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Medline publication type Research Support, N.I.H., Extramural
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Medline publication type Research Support, Non-U.S. Gov't
700 ## - ADDED ENTRY--PERSONAL NAME
Local Authors Sheikh, Farooq
790 ## - Authors
All authors Cameron AM, Chivukula RR, Clark KR, Creamer TJ, Hwang HW, Karhadkar S, Knabel MK, Mendell JT, Montgomery RA, Ramachandran K, Sheikh F, Torbenson M, Warren DS
856 ## - ELECTRONIC LOCATION AND ACCESS
DOI <a href="http://dx.doi.org/10.1371/journal.pone.0124411">http://dx.doi.org/10.1371/journal.pone.0124411</a>
Public note http://dx.doi.org/10.1371/journal.pone.0124411
942 ## - ADDED ENTRY ELEMENTS (KOHA)
Koha item type Journal Article
Item type description Article
Holdings
Withdrawn status Lost status Damaged status Not for loan Collection Home library Current library Date acquired Total Checkouts Full call number Barcode Date last seen Price effective from Koha item type
          MedStar Authors Catalog MedStar Authors Catalog 05/24/2016   25923107 25923107 05/24/2016 05/24/2016 Journal Article

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