| Item type |
デフォルトアイテムタイプ_（フル）(1) |
| 公開日 |
2024-12-09 |
| タイトル |
|
|
タイトル |
Integrator complex subunit 6 promotes hepatocellular steatosis via β-catenin-PPARγ axis |
|
言語 |
en |
| 作成者 |
Shiozaki , Minami
Kanno, Keishi
Yonezawa, Sayaka
Otani, Yuichiro
Shigenobu, Yuya
Haratake, Daisuke
Murakami, Eisuke
Oka, Shiro
Ito, Masanori
|
| アクセス権 |
|
|
アクセス権 |
embargoed access |
|
アクセス権URI |
http://purl.org/coar/access_right/c_f1cf |
| 権利情報 |
|
|
言語 |
en |
|
権利情報 |
© 2024. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| 権利情報 |
|
|
言語 |
en |
|
権利情報 |
This is not the published version. Please cite only the published version. |
| 権利情報 |
|
|
言語 |
ja |
|
権利情報 |
この論文は出版社版ではありません。引用の際には出版社版をご確認、ご利用ください。 |
| 主題 |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
Metabolic dysfunction-associated steatotic liver disease |
| 主題 |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
Metabolic dysfunction-associated steatohepatitis |
| 主題 |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
Integrator complex subunit 6 |
| 主題 |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
Lipid metabolism |
| 主題 |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
Adipogenesis |
| 内容記述 |
|
|
内容記述 |
Hepatic adipogenesis has common mechanisms with adipocyte differentiation such as PPARγ involvement and the induction of adipose tissue-specific molecules. A previous report demonstrated that integrator complex subunit 6 (INTS6) is required for adipocyte differentiation. This study aimed to investigate INTS6 expression and its role in hepatic steatosis progression. The expression of INTS6 and PPARγ was examined in the liver of a mouse model of steatohepatitis and in paired liver biopsy samples from 11 patients with severe obesity and histologically proven metabolic dysfunction associated steatohepatitis (MASH) before and one year after bariatric surgery. To induce hepatocellular steatosis in vitro, an immortalized human hepatocyte cell line Hc3716 was treated with free fatty acids. In the steatohepatitis mouse model, we observed hepatic induction of INTS6, PPARγ, and adipocyte-specific genes. In contrast, β-catenin which negatively regulates PPARγ was reduced. Biopsied human livers demonstrated a strong positive correlation (r2 = 0.8755) between INTS6 and PPARγ mRNA levels. After bariatric surgery, gene expressions of PPARγ, FABP4, and CD36 were mostly downregulated. In our in vitro experiments, we observed a concentration-dependent increase in Oil Red O staining in Hc3716 cells after treatment with the free fatty acids. Alongside this change, the expression of INTS6, PPARγ, and adipocyte-specific genes was induced. INTS6 knockdown using siRNA significantly suppressed cellular lipid accumulation together with induction of β-catenin and PPARγ downregulation. Collectively, INTS6 expression closely correlates with PPARγ. INTS6 suppression significantly reduced hepatocyte steatosis via β-catenin-PPARγ axis, indicating that INTS6 could be a novel therapeutic target for treating MASH. |
|
言語 |
en |
| 出版者 |
|
|
出版者 |
Elsevier |
|
言語 |
en |
| 言語 |
|
|
言語 |
eng |
| 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 |
| 出版タイプ |
|
|
出版タイプ |
AM |
|
出版タイプResource |
http://purl.org/coar/version/c_ab4af688f83e57aa |
| 関連情報 |
|
|
関連タイプ |
isVersionOf |
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
https://doi.org/10.1016/j.bbalip.2024.159532 |
| 開始ページ |
|
|
開始ページ |
159532 |
| 書誌情報 |
en : Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
巻 1869,
号 7,
p. 159532,
発行日 2024-07-07
|
| 旧ID |
55832 |
| 備考 |
The full-text file will be made open to the public on 7 July 2025 in accordance with publisher's 'Terms and Conditions for Self-Archiving' |
BBAMCBL_1869_159532.pdf (689.4 KB)
