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DNA Methylation of PTGIS Enhances Hepatic Stellate Cells Activation and Liver Fibrogenesis

Overview of attention for article published in Frontiers in Pharmacology, May 2018
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Title
DNA Methylation of PTGIS Enhances Hepatic Stellate Cells Activation and Liver Fibrogenesis
Published in
Frontiers in Pharmacology, May 2018
DOI 10.3389/fphar.2018.00553
Pubmed ID
Authors

Xue-yin Pan, Yang Yang, Hong-wu Meng, Hai-di Li, Xin Chen, Hui-min Huang, Fang-tian Bu, Hai-xia Yu, Qin Wang, Cheng Huang, Xiao-ming Meng, Jun Li

Abstract

The activation of hepatic stellate cells (HSCs) is a central event in the progression of liver fibrosis. Multiple studies proved that DNA methylation might accelerate HSCs activation. However, the specific pathogenesis of liver fibrosis remains not fully addressed. Our laboratory performed Genome methylation screening to find out the methylated gene in mice with liver fibrosis. The pilot experiments showed that the promoter of prostacyclin synthase (PTGIS) gene was hypermethylated in CCl4-induced liver fibrosis mouse model. Moreover, the down-regulated PTGIS expression can be restored by DNMTs-RNAi and 5-aza-2-deoxycytidine (5-azadC), an inhibitor of DNA methyltransferase (DNMTs). Methylation-specific PCR (MSP) showed that the methylation status of PTGIS in HSC-T6 cells cultures with TGF-β1 (10 ng/mL) was elevated compared with control group. Chromatin immunoprecipitation (ChIP) assay indicated that PTGIS methylation was mainly induced by DNMT1 and DNMT3b. We further investigated the function of PTGIS in liver fibrosis by Recombinant Hepatic-adeno-associated virus (rAAV8)-PTGIS overexpression. The data indicated that overexpression of PTGIS in mouse liver accompanied by elevated apoptosis-related proteins expression in primary HSCs. Conversely, PTGIS silencing mediated by RNAi enhanced the expression of α-SMA and COL1a1 in vitro. Those results illustrated that adding PTGIS expression inhibits the activation of HSCs and alleviates liver fibrosis. Therefore, our study unveils the role of PTGIS in HSCs activation, which may provide a possible explanation for CCl4-mediated liver fibrosis.

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The data shown below were compiled from readership statistics for 10 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 10 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 3 30%
Student > Doctoral Student 2 20%
Researcher 2 20%
Professor 1 10%
Student > Master 1 10%
Other 1 10%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 6 60%
Medicine and Dentistry 4 40%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 07 June 2018.
All research outputs
#20,520,426
of 23,088,369 outputs
Outputs from Frontiers in Pharmacology
#10,318
of 16,441 outputs
Outputs of similar age
#290,330
of 330,907 outputs
Outputs of similar age from Frontiers in Pharmacology
#238
of 399 outputs
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So far Altmetric has tracked 16,441 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.0. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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We're also able to compare this research output to 399 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.