| Item type |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2025-04-15 |
| タイトル |
|
|
タイトル |
Induction of phospholipase A2 group 4C by HCV infection regulates lipid droplet formation |
|
言語 |
en |
| 言語 |
|
|
言語 |
eng |
| キーワード |
|
|
主題 |
HCV |
| キーワード |
|
|
主題 |
liver steatosis |
| キーワード |
|
|
主題 |
human hepatocyte chimeric mice |
| キーワード |
|
|
主題 |
lipidome analysis |
| キーワード |
|
|
主題 |
PLA2G4C |
| 資源タイプ |
|
|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
journal article |
| アクセス権 |
|
|
アクセス権 |
open access |
|
アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
| 著者 |
Ito, Masahiko
Liu, Jie
Fukasawa, Masayoshi
Tsutsumi, Koji
Kanegae , Yumi
Setou, Mitsutoshi
Kohara, Michinori
Suzuki, Tetsuro
|
| 書誌情報 |
en : JHEP Reports
巻 7,
号 1,
p. 101225,
発行日 2024-12-16
|
| 出版者 |
|
|
出版者 |
Elsevier |
|
言語 |
en |
| 権利 |
|
|
権利情報 |
(C) 2024 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL). This is an open access article under the CC BYNC- ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| 抄録 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
Background & Aims: Hepatic steatosis, characterized by lipid accumulation in hepatocytes, is a key diagnostic feature in patients with chronic hepatitis C virus (HCV) infection. This study aimed to clarify the involvement of phospholipid metabolic pathways in the pathogenesis of HCV-induced steatosis.
Methods: The expression and distribution of lipid species in the livers of human liver chimeric mice were analyzed using imaging mass spectrometry. Triglyceride accumulation and lipid droplet formation were studied in phospholipase A2 group 4C (PLA2G4C) knockout or overexpressing cells.
Results: Imaging mass spectrometry of the infected mouse model revealed increased lysophosphatidylcholine levels and decreased phosphatidylcholine levels in HCV-positive regions of the liver. Among the transcripts associated with phosphatidylcholine biosynthesis, upregulation of PLA2G4C mRNA was most pronounced following HCV infection. Activation of the transcription factor NF-jB and upregulation of c-Myc were important for activation of PLA2G4C transcription by HCV infection and expression of the viral proteins Core-NS2. The amount and size of lipid droplets were reduced in PLA2G4C-knockout cells. Inhibition of NF-jB or c-Myc activity suppressed lipid droplet formation in HCV-infected cells. HCV infection promoted the stabilization of lipid droplets, but this stability was reduced in PLA2G4C-knockout cells. Overexpression of PLA2G4C decreased the levels of phosphatidylcholine species in the lipid droplet fraction and led to lower levels of key factors involved in lipolysis (breakdown of triglycerides into glycerol and free fatty acids), such as ATGL, PLIN1 and ABHD5 on the lipid droplets.
Conclusions: HCV infection markedly increases PLA2G4C expression. This may alter the phospholipid composition of the lipid droplet membrane, leading to stabilization and enlargement of the droplets. |
| 注記 |
|
|
内容記述 |
令和6年 浜松医科大学優秀論文賞：優秀論文賞
受賞者：伊藤 昌彦 |
| EISSN |
|
|
収録物識別子タイプ |
EISSN |
|
収録物識別子 |
2589-5559 |
| PubMed番号 |
|
|
関連タイプ |
isIdenticalTo |
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|
識別子タイプ |
PMID |
|
|
関連識別子 |
39802806 |
| 出版社DOI |
|
|
関連タイプ |
isIdenticalTo |
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
https://doi.org/10.1016/j.jhepr.2024.101225 |
| 著者版フラグ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
JHEP Rep-7-101225.pdf (1.5 MB)
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