| ○種別 (必須): | □ | 学術論文 (審査論文)
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| ○言語 (必須): | □ | 英語
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| ○審査 (推奨): |
| ○カテゴリ (推奨): |
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| ○学究種別 (推奨): |
| ○組織 (推奨): |
| ○著者 (必須): | 1. | (英) Birukawa Naoko Kubo (日) (読)
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| 2. | (英) Murase Kazuyuki (日) (読)
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| 3. | 佐藤 康史 ([徳島大学.大学院医歯薬学研究部.医学域.連携研究部門(医学域).寄附講座系(医学域).地域消化器・総合内科学])
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| 4. | (英) Kosaka Akemi (日) (読)
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| 5. | (英) Yoneda Akihiro (日) (読)
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| 6. | (英) Nishita Hiroki (日) (読)
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| 7. | (英) Fujita Ryosuke (日) (読)
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| 8. | (英) Nishimura Miyuki (日) (読)
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| 9. | (英) Ninomiya Takafumi (日) (読)
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| 10. | (英) Kajiwara Keiko (日) (読)
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| 11. | (英) Miyazaki Miyono (日) (読)
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| 12. | (英) Nakashima Yusuke (日) (読)
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| 13. | (英) Ota Sigenori (日) (読)
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| 14. | (英) Murakami Yuya (日) (読)
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| 15. | (英) Tanaka Yasunobu (日) (読)
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| 16. | (英) Minomi Kenjiro (日) (読)
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| 17. | (英) Tamura Yasuaki (日) (読)
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| 18. | (英) Niitsu Yoshiro (日) (読)
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| ○題名 (必須): | □ | (英) Activated hepatic stellate cells are dependent on self-collagen, cleaved by membrane type 1 matrix metalloproteinase for their growth. (日)
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| ○要約 (任意): | □ | (英) Stellate cells are distributed throughout organs, where, upon chronic damage, they become activated and proliferate to secrete collagen, which results in organ fibrosis. An intriguing property of hepatic stellate cells (HSCs) is that they undergo apoptosis when collagen is resolved by stopping tissue damage or by treatment, even though the mechanisms are unknown. Here we disclose the fact that HSCs, normal diploid cells, acquired dependence on collagen for their growth during the transition from quiescent to active states. The intramolecular RGD motifs of collagen were exposed by cleavage with their own membrane type 1 matrix metalloproteinase (MT1-MMP). The following evidence supports this conclusion. When rat activated HSCs (aHSCs) were transduced with siRNA against the collagen-specific chaperone gp46 to inhibit collagen secretion, the cells underwent autophagy followed by apoptosis. Concomitantly, the growth of aHSCs was suppressed, whereas that of quiescent HSCs was not. These in vitro results are compatible with the in vivo observation that apoptosis of aHSCs was induced in cirrhotic livers of rats treated with siRNAgp46. siRNA against MT1-MMP and addition of tissue inhibitor of metalloproteinase 2 (TIMP-2), which mainly inhibits MT1-MMP, also significantly suppressed the growth of aHSCs in vitro. The RGD inhibitors echistatin and GRGDS peptide and siRNA against the RGD receptor V1 resulted in the inhibition of aHSCs growth. Transduction of siRNAs against gp46, V1, and MT1-MMP to aHSCs inhibited the survival signal of PI3K/AKT/IB. These results could provide novel antifibrosis strategies. (日)
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| ○キーワード (推奨): | 1. | (英) Animals (日) (読)
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| 2. | (英) Apoptosis (日) (読)
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| 3. | 細胞増殖·分化 (cell proliferation and differentiation)
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| 4. | (英) Cell Survival (日) (読)
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| 5. | コラーゲン (collagen)
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| 6. | (英) HSP47 Heat-Shock Proteins (日) (読)
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| 7. | (英) Hepatic Stellate Cells (日) (読)
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| 8. | (英) Humans (日) (読)
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| 9. | (英) I-kappa B Proteins (日) (読)
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| 10. | (英) Integrins (日) (読)
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| 11. | (英) Liver Cirrhosis (日) (読)
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| 12. | (英) Matrix Metalloproteinase 14 (日) (読)
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| 13. | (英) Matrix Metalloproteinase Inhibitors (日) (読)
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| 14. | ノックアウトマウス (knockout mice)
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| 15. | (英) Oligopeptides (日) (読)
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| 16. | (英) Phosphatidylinositol 3-Kinases (日) (読)
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| 17. | (英) Proto-Oncogene Proteins c-akt (日) (読)
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| 18. | (英) RNA, Small Interfering (日) (読)
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| 19. | (英) Rats (日) (読)
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| 20. | (英) Rats, Sprague-Dawley (日) (読)
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| 21. | シグナル伝達 (signal transduction)
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| 22. | (英) Tissue Inhibitor of Metalloproteinase-1 (日) (読)
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| ○発行所 (推奨): |
| ○誌名 (必須): | □ | The Journal of Biological Chemistry ([The American Society for Biochemistry and Molecular Biology])
(pISSN: 0021-9258, eISSN: 1083-351X)
| ○ISSN (任意): | □ | 1083-351X
ISSN: 0021-9258
(pISSN: 0021-9258, eISSN: 1083-351X) Title: The Journal of biological chemistryTitle(ISO): J Biol ChemPublisher: American Society for Biochemistry and Molecular Biology (NLM Catalog)
(Scopus)
(CrossRef)
(Scopus information is found. [need login]) | [継承] |
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| ○巻 (必須): | □ | 289
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| ○号 (必須): | □ | 29
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| ○頁 (必須): | □ | 20209 20221
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| ○都市 (任意): |
| ○年月日 (必須): | □ | 西暦 2014年 5月 27日 (平成 26年 5月 27日)
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| ○URL (任意): |
| ○DOI (任意): | □ | 10.1074/jbc.M113.544494 (→Scopusで検索)
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| ○PMID (任意): | □ | 24867951 (→Scopusで検索)
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| ○備考 (任意): | 1. | (英) PublicationType: Journal Article (日)
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