类有机物
脂肪性肝炎
脂肪肝
酒精性肝病
癌症研究
肝细胞癌
下调和上调
医学
内科学
肝星状细胞
生物
病理
细胞生物学
基因
内分泌学
肝硬化
遗传学
疾病
作者
Mohamed Elbadawy,Megumi Yamanaka,Yuta Goto,Kimika Hayashi,Ryouichi Tsunedomi,Shoichi Hazama,Hiroaki Nagano,Toshinori Yoshida,Makoto Shibutani,Ryo Ichikawa,Jin Nakahara,Tsutomu Omatsu,Tetsuya Mizutani,Yukie Katayama,Yuta Shinohara,Amira Abugomaa,Masahiro Kaneda,Hideyuki Yamawaki,Tatsuya Usui,Kenji Sasaki
出处
期刊:Biomaterials
[Elsevier]
日期:2020-04-01
卷期号:237: 119823-119823
被引量:50
标识
DOI:10.1016/j.biomaterials.2020.119823
摘要
Non-alcoholic steatohepatitis (NASH) is associated with liver fibrosis and cirrhosis, which eventually leads to hepatocellular carcinoma. Although several animal models were developed to understand the mechanisms of NASH pathogenesis and progression, it remains obscure. A 3D organoid culture system can recapitulate organ structures and maintain gene expression profiles of original tissues. We therefore tried to generate liver organoids from different degrees [defined as mild (NASH A), moderate (NASH B) and severe (NASH C)] of methionine- and choline-deficient diet-induced NASH model mice and analyzed the difference of their architecture, cell components, organoid-forming efficacy, and gene expression profiles. Organoids from each stage of NASH model mice were successfully generated. Interestingly, epithelial-mesenchymal transition was observed in NASH C organoids. Expression of Collagen I and an activated hepatic stellite cell marker, α-sma was upregulated in the liver organoids from NASH B and C mice. The analysis of RNA sequencing revealed that several novel genes were upregulated in all NASH liver organoids. These results suggest that our generated liver organoids from different stages of NASH diseased mice might become a useful tool for in vitro studies of the molecular mechanism of NASH development and also for identifying novel biomarkers for early diagnosis of NASH disease.
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