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Lipid-Induced Hepatocyte-Derived Extracellular Vesicles Regulate Hepatic Stellate Cells via MicroRNA Targeting Peroxisome Proliferator-Activated Receptor-γ

Overview of attention for article published in Cellular and Molecular Gastroenterology and Hepatology, July 2015
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  • Good Attention Score compared to outputs of the same age (71st percentile)
  • Above-average Attention Score compared to outputs of the same age and source (54th percentile)

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Title
Lipid-Induced Hepatocyte-Derived Extracellular Vesicles Regulate Hepatic Stellate Cells via MicroRNA Targeting Peroxisome Proliferator-Activated Receptor-γ
Published in
Cellular and Molecular Gastroenterology and Hepatology, July 2015
DOI 10.1016/j.jcmgh.2015.07.007
Pubmed ID
Authors

Davide Povero, Nadia Panera, Akiko Eguchi, Casey D. Johnson, Bettina G. Papouchado, Lucas de Araujo Horcel, Eva M. Pinatel, Anna Alisi, Valerio Nobili, Ariel E. Feldstein

Abstract

Hepatic stellate cells (HSCs) play a key role in liver fibrosis in various chronic liver disorders including nonalcoholic fatty liver disease (NAFLD). The development of liver fibrosis requires a phenotypic switch from quiescent to activated HSCs. The triggers for HSCs activation in NAFLD remain poorly understood. We investigated the role and molecular mechanism of extracellular vesicles (EVs) released by hepatocytes during lipotoxicity in modulation of HSC phenotype. EVs were isolated from fat-laden hepatocytes by differential centrifugation and incubated with HSCs. EV internalization and HSCs activation, migration and proliferation were assessed. Loss- and gain-of-functions studies were performed to explore the potential role of PPAR-γ-targeting miRNAs carried by EVs into HSC. Hepatocyte-derived EVs released during lipotoxicity are efficiently internalized by HSCs resulting in their activation, as shown by marked up-regulation of pro-fibrogenic genes (Collagen-I, α-SMA and TIMP-2), proliferation, chemotaxis and wound healing responses. These changes were associated with miRNAs shuttled by EVs and suppression of PPAR-γ expression in HSC. Hepatocyte-derived EVs miRNA content included various miRNAs that are known inhibitors of PPAR-γ expression with miR-128-3p being the most effectively transferred. Furthermore loss- and gain-of-function studies identified miR-128-3p as a central modulator of the effects of EVs on PPAR-γ inhibition and HSC activation. Our findings demonstrate a link between fat-laden hepatocyte-derived EVs and liver fibrosis and have potential implications for the development of novel anti-fibrotic targets for NAFLD and other fibrotic diseases.

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The data shown below were collected from the profiles of 6 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 123 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 123 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 26 21%
Researcher 23 19%
Student > Master 13 11%
Student > Doctoral Student 10 8%
Student > Bachelor 9 7%
Other 13 11%
Unknown 29 24%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 31 25%
Medicine and Dentistry 24 20%
Agricultural and Biological Sciences 19 15%
Pharmacology, Toxicology and Pharmaceutical Science 5 4%
Chemistry 3 2%
Other 7 6%
Unknown 34 28%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 5. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 20 January 2016.
All research outputs
#7,301,044
of 25,371,288 outputs
Outputs from Cellular and Molecular Gastroenterology and Hepatology
#502
of 1,142 outputs
Outputs of similar age
#78,848
of 275,159 outputs
Outputs of similar age from Cellular and Molecular Gastroenterology and Hepatology
#10
of 22 outputs
Altmetric has tracked 25,371,288 research outputs across all sources so far. This one has received more attention than most of these and is in the 71st percentile.
So far Altmetric has tracked 1,142 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.3. This one has gotten more attention than average, scoring higher than 55% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 275,159 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 71% of its contemporaries.
We're also able to compare this research output to 22 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 54% of its contemporaries.