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ID 119324
タイトル別表記
X box-binding protein1を介した小胞体ストレス応答不全は非アルコール性脂肪肝炎モデルマウスにおける肝部分切除後の肝再生不良の主要な要因である
著者
宮崎, 克己 徳島大学大学院医学研究科(医学専攻)
徳田, 和憲 Tokushima University
キーワード
Nonalcoholic steatohepatitis
hepatectomy
liver regeneration
endoplasmic reticulum stress response
lipid droplets
資料タイプ
学位論文
抄録
Background
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Poor regeneration after hepatectomy in NAFLD is well recognized, but the mechanism is unclear. Endoplasmic reticulum (ER) stress plays an important role in the development of NAFLD. Here, we show that an impaired ER stress response contributes to poor liver regeneration in partially hepatectomized mice.
Methods
Non-alcoholic fatty liver (NAFL) or non-alcoholic steatohepatitis (NASH) was induced in mice using our patented feed and 70% partial hepatectomy (PH) was performed. Mice were sacrificed 0, 4, 8, 24, or 48 hours, or 7 days after PH, and liver regeneration and the mRNA expression of ER stress markers were assessed.
Results
NAFLD activity score was calculated as 4–6 points for NAFL and 7 points for NASH. NASH was characterized by inflammation and high ER stress marker expression before PH. After PH, NASH mice showed poorer liver regeneration than controls. High expression of proinflammatory cytokine genes was present in NASH mice 4 hours after PH. Xbp1-s mRNA expression was high in control and NAFL mice after PH, but no higher in NASH mice.
Conclusions
Dysfunction of the ER stress response might be a cause of poor liver regeneration in NASH.
掲載誌名
Journal of Hepato-Biliary-Pancreatic Sciences
ISSN
18686974
18686982
cat書誌ID
AA12507209
出版者
Japanese Society of Hepato‐Biliary‐Pancreatic Surgery|Wiley
29
12
開始ページ
1241
終了ページ
1252
発行日
2022-03-24
備考
内容要旨・審査要旨・論文本文の公開
本論文は,著者Katsuki Miyazaki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。
This is the peer reviewed version of the following article: Miyazaki, K., Saito, Y.,Ichimura-Shimizu, M., Imura, S., Ikemoto, T., Yamada, S., Tokuda, K., Morine, Y., Tsuneyama, K., Shimada, M., (2022), Defective endoplasmic reticulum stress response via X box-binding protein 1 is a major cause of poor liver regeneration after partial hepatectomy in mice with non-alcoholic steatohepatitis. Journal of Hepato-Biliary-Pancreatic Sciences, 29, 12, 1241-1252., which has been published in final form at https://doi.org/10.1002/jhbp.1142. 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.
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第3791号
学位記番号
甲医第1604号
学位授与年月日
2024-03-21
学位名
博士(医学)
学位授与機関
徳島大学
部局
医学系
病院