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Because PPAR alpha is a central regulator of triglyceride homeostasis and mediates hepatocarcinogenesis in rodents, we determined whether PPAR alpha contributes to HCV core protein-induced diseases. We generated PPAR alpha-homozygous, -heterozygous, and -null mice with liver-specific transgenic expression of the core protein gene (Ppara(+/+):HCVcpTg, Ppara(-/-):HCVcpTg, and Ppara(-/-):HCVcpTg mice. Severe steatosis was unexpectedly observed only in Ppara+/+:HCVcpTg mice, which resulted from enhanced fatty acid uptake and decreased mitochondrial beta-oxidation due to breakdown of mitochondrial outer membranes. Interestingly, HCC developed in approximately 35% of 24-month-old Pparat(+/+): HCVcpTg mice, but tumors were not observed in the other genotypes. These phenomena were found to be closely associated with sustained PPAR alpha activation. In Ppara(+/-):HCVcpTg mice, PPAR alpha activation and the related changes did not occur despite the presence of a functional Ppara allele. However, long-term treatment of these mice with clofibrate, a PPAR alpha activator, induced HCC with mitochondrial abnormalities and hepatic steatosis. Thus, our results indicate that persistent activation of PPAR alpha is essential for the pathogenesis of hepatic steatosis and HCC induced by HCV infection."}]}, "item_creator": {"attribute_name": "著者", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "Tanaka, N", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "8313", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Moriya, K", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "8314", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Kiyosawa, K", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "8315", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Koike, K", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "8316", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Gonzalez, FJ", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "8317", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Aoyama, T", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "8318", "nameIdentifierScheme": "WEKO"}]}]}, "item_files": {"attribute_name": "ファイル情報", "attribute_type": "file", "attribute_value_mlt": [{"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2015-09-24"}], "displaytype": "detail", "download_preview_message": "", "file_order": 0, "filename": "33594RG-RV2[1].pdf", "filesize": [{"value": "220.9 kB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_note", "mimetype": "application/pdf", "size": 220900.0, "url": {"label": "33594RG-RV2[1].pdf", "url": "https://soar-ir.repo.nii.ac.jp/record/3969/files/33594RG-RV2[1].pdf"}, "version_id": "ef7bb87a-2795-48f7-ac09-42e14e49ba62"}]}, "item_language": {"attribute_name": "言語", "attribute_value_mlt": [{"subitem_language": "eng"}]}, "item_resource_type": {"attribute_name": "資源タイプ", "attribute_value_mlt": [{"resourcetype": "journal article", "resourceuri": "http://purl.org/coar/resource_type/c_6501"}]}, "item_title": "PPAR alpha activation is essential for HCV core protein-induced hepatic steatosis and hepatocellular carcinoma in mice", "item_titles": {"attribute_name": "タイトル", "attribute_value_mlt": [{"subitem_title": "PPAR alpha activation is essential for HCV core protein-induced hepatic steatosis and hepatocellular carcinoma in mice", "subitem_title_language": "en"}]}, "item_type_id": "6", "owner": "1", "path": ["462"], "permalink_uri": "http://hdl.handle.net/10091/1161", "pubdate": {"attribute_name": "PubDate", "attribute_value": "2008-09-18"}, "publish_date": "2008-09-18", "publish_status": "0", "recid": "3969", "relation": {}, "relation_version_is_last": true, "title": ["PPAR alpha activation is essential for HCV core protein-induced hepatic steatosis and hepatocellular carcinoma in mice"], "weko_shared_id": -1}
PPAR alpha activation is essential for HCV core protein-induced hepatic steatosis and hepatocellular carcinoma in mice
http://hdl.handle.net/10091/1161
http://hdl.handle.net/10091/1161bed9b14f-0b32-4123-8a31-09f1b2fd8295
名前 / ファイル | ライセンス | アクション |
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2008-09-18 | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | PPAR alpha activation is essential for HCV core protein-induced hepatic steatosis and hepatocellular carcinoma in mice | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源 | http://purl.org/coar/resource_type/c_6501 | |||||
タイプ | journal article | |||||
著者 |
Tanaka, N
× Tanaka, N× Moriya, K× Kiyosawa, K× Koike, K× Gonzalez, FJ× Aoyama, T |
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出版者 | ||||||
出版者 | AMER SOC CLINICAL INVESTIGATION INC | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | JOURNAL OF CLINICAL INVESTIGATION. 118(2):683-694(2008) | |||||
書誌情報 |
JOURNAL OF CLINICAL INVESTIGATION 巻 118, 号 2, p. 683-694, 発行日 2008-02 |
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資源タイプ(コンテンツの種類) | ||||||
内容記述タイプ | Other | |||||
内容記述 | Article | |||||
ISSN | ||||||
収録物識別子タイプ | PISSN | |||||
収録物識別子 | 0021-9738 | |||||
書誌レコードID | ||||||
収録物識別子タイプ | NCID | |||||
収録物識別子 | AA00695520 | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | https://doi.org/10.1172/JCI33594 | |||||
関連名称 | 10.1172/JCI33594 | |||||
出版タイプ | ||||||
出版タイプ | AM | |||||
出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||
WoS | ||||||
表示名 | Web of Science | |||||
URL | http://gateway.isiknowledge.com/gateway/Gateway.cgi?&GWVersion=2&SrcAuth=ShinshuUniv&SrcApp=ShinshuUniv&DestLinkType=FullRecord&DestApp=WOS&KeyUT=000252777400035 |