| Item type |
文献 / Documents(1) |
| 公開日 |
2024-05-13 |
| アクセス権 |
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アクセス権 |
open access |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_db06 |
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資源タイプ |
doctoral thesis |
| 出版社版DOI |
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関連識別子 |
https://doi.org/10.1002/path.6204 |
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関連名称 |
10.1002/path.6204 |
| 出版タイプ |
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出版タイプ |
NA |
|
出版タイプResource |
http://purl.org/coar/version/c_be7fb7dd8ff6fe43 |
| タイトル |
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|
タイトル |
Brain-derived neurotrophic factor knock-out mice develop non-alcoholic steatohepatitis |
| タイトル別表記 |
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その他のタイトル |
BDNF-KO mice develop NASH |
| タイトル別表記 |
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その他のタイトル |
脳由来神経栄養因子のノックアウトマウスは非アルコール性脂肪肝炎を発症する |
| 著者 |
(市村)清水, 真祐子
コジマ, マサミ
スズキ, シンゴ
ミヤタ, ミサキ
オサキ, ユイ
マツイ, コノミ
ミズイ, トシユキ
常山, 幸一
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| 抄録 |
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内容記述 |
While brain-derived neurotrophic factor (BDNF), which is a growth factor associated with cognitive improvement and the alleviation of depression symptoms, is known to regulate food intake and body weight, the role of BDNF in peripheral disease is not fully understood. Here, we show that reduced BDNF expression is associated with weight gain and the chronic liver disease nonalcoholic steatohepatitis (NASH). At 10 months of age, BDNF-heterozygous (BDNF+/-) mice develop symptoms of NASH: centrilobular/perivenular steatosis, lobular inflammation with infiltration of neutrophils, ballooning hepatocytes, and fibrosis of the liver. Obesity and higher serum levels of glucose and insulin—major pathologic features in human NASH—are dramatic. Dying adipocytes are surrounded by macrophages in visceral fat, suggesting that chronic inflammation occurs in peripheral organs. RNA-seq studies of the liver revealed that the most significantly enriched gene ontology term involves fatty acid metabolic processes and the modulation of neutrophil aggregation, pathologies that well characterise NASH. Gene expression analysis by RNA-seq also suggested that the BDNF+/- mice are under oxidative stress, as indicated by alterations in the expression of the cytochrome P450 family and a reduction in glutathione S-transferase p, an antioxidant enzyme. Histopathologic phenotypes of NASH were also observed in a knock-in mouse (BDNF+/pro), in which the precursor BDNF is inefficiently converted into the mature form of BDNF. Lastly, as BDNF reduction causes overeating and subsequent obesity, a food restriction study was conducted in BDNF+/pro mice. Pair-fed BDNF+/pro mice developed hepatocellular damage and showed infiltration of inflammatory cells including neutrophils in the liver, despite having body weights and blood parameters that were comparable to controls. Collectively, this is the first report demonstrating that reduced BDNF expression plays a role in the pathogenic mechanism of NASH, which is a hepatic manifestation of metabolic syndrome. |
| キーワード |
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主題 |
brain-derived neurotrophic factor |
| キーワード |
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主題 |
nonalcoholic steatohepatitis |
| キーワード |
|
|
主題 |
nonalcoholic fatty liver disease |
| キーワード |
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|
主題 |
liver fibrosis |
| キーワード |
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主題 |
RNA-seq |
| キーワード |
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|
主題 |
gene ontology |
| キーワード |
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|
主題 |
mouse model |
| キーワード |
|
|
主題 |
脳由来神経栄養因子 |
| キーワード |
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|
主題 |
脂肪肝炎 |
| キーワード |
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|
主題 |
脳肝相関 |
| キーワード |
|
|
主題 |
モデルマウス |
| キーワード |
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|
主題 |
MASH |
| 書誌情報 |
en : The Journal of Pathology
巻 261,
号 4,
p. 465-476,
発行日 2023-10-02
|
| 収録物ID |
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収録物識別子タイプ |
ISSN |
|
収録物識別子 |
10969896 |
| 収録物ID |
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収録物識別子タイプ |
ISSN |
|
収録物識別子 |
00223417 |
| 収録物ID |
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収録物識別子タイプ |
NCID |
|
収録物識別子 |
AA11628456 |
| 収録物ID |
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|
収録物識別子タイプ |
NCID |
|
収録物識別子 |
AA00704326 |
| 出版者 |
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|
出版者 |
Wiley |
| 備考 |
|
|
値 |
内容要旨・審査要旨・論文本文の公開
本論文は，著者Mayuko Ichimura-Shimizuの学位論文として提出され，学位審査・授与の対象となっている。 |
| 権利情報 |
|
|
権利情報 |
This is the peer reviewed version of the following article: Ichimura-Shimizu, M., Kojima, M., Suzuki, S., Miyata, M., Osaki, Y., Matsui, K., Mizui, T., Tsuneyama, K., (2023), Brain-derived neurotrophic factor knock-out mice develop non-alcoholic steatohepatitis. The Journal of Pathology, 261, 4, 465-476., which has been published in final form at https://doi.org/10.1002/path.6204. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited. |
| EID |
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識別子 |
406325 |
| 言語 |
|
|
言語 |
eng |
| 報告番号 |
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学位授与番号 |
乙第2131号 |
| 学位記番号 |
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|
値 |
乙医第1765号 |
| 学位授与年月日 |
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|
学位授与年月日 |
2024-02-22 |
| 学位名 |
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学位名 |
博士（医学） |
| 学位授与機関 |
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|
学位授与機関名 |
徳島大学 |
o2131_abstract.pdf (129 KB)
