Evidence map›Paper›PMID 30954078›Full record

ArticleLipids in health and disease2019

Perilipin 5 alleviates HCV NS5A-induced lipotoxic injuries in liver.

Jin Zhang, Xing Gao, Yuan Yuan, Chao Sun, Yuanlin Zhao, Liming Xiao, Ying Yang, Yu Gu, Risheng Yang, Peizhen Hu and 3 more

Open access · goldAbstract read
In one paragraph

Article in Lipids in health and disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.7field-weighted citation impact, top 33% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 17 citations in OpenAlex.

  1. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 1 country.

Jin ZhangState Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, No.169, Changle West Road, Xi'an, Shaanxi, 710032, People's Republic of China.
Xing GaoState Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, No.169, Changle West Road, Xi'an, Shaanxi, 710032, People's Republic of China.
Yuan YuanState Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, No.169, Changle West Road, Xi'an, Shaanxi, 710032, People's Republic of China.
Chao SunDepartment of Neurology, Tangdu Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, 710032, People's Republic of China.
Yuanlin ZhaoState Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, No.169, Changle West Road, Xi'an, Shaanxi, 710032, People's Republic of China.
Liming XiaoState Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, No.169, Changle West Road, Xi'an, Shaanxi, 710032, People's Republic of China.
Ying YangState Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, No.169, Changle West Road, Xi'an, Shaanxi, 710032, People's Republic of China.
Yu GuState Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, No.169, Changle West Road, Xi'an, Shaanxi, 710032, People's Republic of China.
Risheng YangState Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, No.169, Changle West Road, Xi'an, Shaanxi, 710032, People's Republic of China.
Peizhen HuState Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, No.169, Changle West Road, Xi'an, Shaanxi, 710032, People's Republic of China.
Lijun ZhangDepartment of Clinical Laboratory Medicine, Tangdu Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, 710038, People's Republic of China.
Chao WangDepartment of Pathology, The General Hospital of Western Theater Command, No. 270, Tianhui Road, Rongdu Avenue, Chengdu, 610083, People's Republic of China. wang_chao1987@126.com.
Jing YeState Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, No.169, Changle West Road, Xi'an, Shaanxi, 710032, People's Republic of China. yejing@fmmu.edu.cn.
Air Force Medical University · CNXijing Hospital · CNChengdu Military General Hospital · CN

Funding

National Natural Science Foundation of China 31671416National Natural Science Foundation of China 81572471National Natural Science Foundation of China 81670792
6 · The paper itself

Abstract

backgroundThe homeostasis of lipid droplets (LDs) plays a crucial role in maintaining the physical metabolic processes in cells, and is regulated by many LD-associated proteins, including perilipin 5 (Plin5) in liver. As the putative sites of hepatitis C virus (HCV) virion assembly, LDs are vital to viral infection. In addition, the hepatic LD metabolism can be disturbed by non-structural HCV proteins, such as NS5A, but the details are still inexplicit.

methodsHCV NS5A was overexpressed in the livers and hepatocytes of wild-type and Plin5-null mice. BODIPY 493/503 and oil red O staining were used to detect the lipid content in mouse livers and hepatocytes. The levels of lipids, lipid peroxidation and inflammation biomarkers were further determined. Immunofluorescence assay and co-immunoprecipitation assay were performed to investigate the relationship of Plin5 and NS5A.

resultsOne week after adenovirus injection, livers expressing NS5A showed more inflammatory cell aggregation and more severe hepatic injuries in Plin5-null mice than in control mice, which was consistent with the increased serum levels of IL-2 and TNF-α (P < 0.05) observed in Plin5-null mice. Moreover, Plin5 deficiency in the liver and hepatocytes aggravated the elevation of MDA and 4-HNE levels induced by NS5A expression (P < 0.01). The triglyceride (TG) content was increased approximately 25% by NS5A expression in the wild-type liver and hepatocytes but was unchanged in the Plin5-null liver and hepatocytes. More importantly, Plin5 deficiency in the liver and hepatocytes exacerbated the elevation of non-esterified fatty acids (NEFAs) stimulated by NS5A expression (P < 0.05 and 0.01 respectively). Using triacsin C to block acyl-CoA biosynthesis, we found that Plin5 deficiency aggravated the NS5A-induced lipolysis of TG. In contrast, Plin5 overexpression in HepG2 cells ameliorated the NS5A-induced lipolysis and lipotoxic injuries. Immunofluorescent staining demonstrated that NS5A expression stimulated the targeting of Plin5 to the surface of the LDs in hepatocytes without altering the protein levels of Plin5. By co-IP, we found that the N-terminal domain (aa 32-128) of Plin5 was pivotal for its binding with NS5A.

conclusionsOur data highlight a protective role of Plin5 against hepatic lipotoxic injuries induced by HCV NS5A, which is helpful for understanding the steatosis and injuries in liver during HCV infection.

Indexed as

Acyl Coenzyme AAdenoviridaeAnimalsDisease Models, AnimalFatty LiverGene Expression Regulation, ViralHepacivirusHepatitis CHepatocytesHumansLipid DropletsLipid MetabolismLipolysisLiverMicePerilipin-5Acyl Coenzyme ANS-5 protein, hepatitis C virusPerilipin-5RNA-Dependent RNA Polymerasetriacsin CTriazenesTriglyceridesTumor Necrosis Factor-alphaViral Nonstructural ProteinsHepatitis C virusLipid dropletLipolysisNonstructural protein 5APerilipin 5

Identifiers

PMID30954078
PMCPMC6451786
OpenAlexW2945343279

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.