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Geranylgeranylacetone attenuates fibrogenic activity and induces apoptosis in cultured human hepatic stellate cells and reduces liver fibrosis in carbon tetrachloride-treated mice

Overview of attention for article published in BMC Gastroenterology, February 2018
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Title
Geranylgeranylacetone attenuates fibrogenic activity and induces apoptosis in cultured human hepatic stellate cells and reduces liver fibrosis in carbon tetrachloride-treated mice
Published in
BMC Gastroenterology, February 2018
DOI 10.1186/s12876-018-0761-7
Pubmed ID
Authors

Takemasa Senoo, Ryu Sasaki, Yuko Akazawa, Tatsuki Ichikawa, Satoshi Miuma, Hisamitsu Miyaaki, Naota Taura, Kazuhiko Nakao

Abstract

Geranylgeranylacetone (GGA), an anti-ulcer drug widely used in Japan, has attracted interest because of its various therapeutic effects. Therefore, we investigated the effects of GGA on human hepatic stellate cells (HSCs) in vitro and in a mouse model of liver fibrosis. LX2, an immortalized human HSC line, was cultured and treated with GGA at concentrations up to 0.5 mM. After GGA treatment, changes in cellular morphology, apoptosis, and fibrosis-related gene expression were assessed. Male C57BL/6 J mouse model of carbon tetrachloride (CCl4)-induced liver fibrosis was treated with GGA. Liver fibrosis was evaluated using Sirius red staining and immunohistochemistry for α-smooth muscle actin (SMA). GGA decreased the density of LX2 and primary human hepatic stellate cells but not that of HepG2 cells (a human hepatoma cell line), which was employed as control. In addition, GGA decreased the expression of fibrogenic genes and increased that of C/EBP homologous protein (CHOP). It also induced endoplasmic reticulum (ER) stress and increased apoptosis. CHOP knockdown, however, failed to suppress the GGA-induced decrease in LX2 cell density, suggesting the involvement of additional molecules in ER stress-associated apoptosis. Expression of death receptor 5, mitogen-activated protein kinase, heat shock protein 70, and Akt, all of which affect the activity of stellate cells, was unchanged in relation to LX2 cell fibrogenic activity. In the mouse model of liver fibrosis, GGA decreased the extent of Sirius red staining and SMA expression. GGA attenuated fibrogenic activity and induced apoptosis in cultured human HSCs, and suppressed liver fibrosis in mice, suggesting its potential as an agent for treating liver fibrosis.

Twitter Demographics

The data shown below were collected from the profiles of 3 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 6 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 6 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 2 33%
Professor > Associate Professor 2 33%
Professor 1 17%
Unspecified 1 17%
Readers by discipline Count As %
Unspecified 2 33%
Agricultural and Biological Sciences 2 33%
Medicine and Dentistry 2 33%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 08 March 2018.
All research outputs
#7,610,721
of 12,617,609 outputs
Outputs from BMC Gastroenterology
#368
of 820 outputs
Outputs of similar age
#150,376
of 273,589 outputs
Outputs of similar age from BMC Gastroenterology
#1
of 1 outputs
Altmetric has tracked 12,617,609 research outputs across all sources so far. This one is in the 37th percentile – i.e., 37% of other outputs scored the same or lower than it.
So far Altmetric has tracked 820 research outputs from this source. They receive a mean Attention Score of 4.6. This one has gotten more attention than average, scoring higher than 51% 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 273,589 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 41st percentile – i.e., 41% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them