| RRC ID |
58666
|
| 著者 |
Asakawa M, Itoh M, Suganami T, Sakai T, Kanai S, Shirakawa I, Yuan X, Hatayama T, Shimada S, Akiyama Y, Fujiu K, Inagaki Y, Manabe I, Yamaoka S, Yamada T, Tanaka S, Ogawa Y.
|
| タイトル |
Upregulation of cancer-associated gene expression in activated fibroblasts in a mouse model of non-alcoholic steatohepatitis.
|
| ジャーナル |
Sci Rep
|
| Abstract |
Non-alcoholic steatohepatitis (NASH), characterized by chronic inflammation and fibrosis, is predicted to be the leading cause of cirrhosis and hepatocellular carcinoma (HCC) in the next decade. Although recent evidence suggests the importance of fibrosis as the strongest determinant of HCC development, the molecular mechanisms underlying NASH-induced carcinogenesis still remain unclear. Here we performed RNA sequencing analysis to compare gene expression profiles of activated fibroblasts prepared from two distinct liver fibrosis models: carbon tetrachloride-induced fibrosis as a model without obesity and HCC and genetically obese melanocortin 4 receptor-deficient (MC4R-KO) mice fed Western diet, which develop steatosis, NASH, and eventually HCC. Our data showed that activated fibroblasts exhibited distinct gene expression patterns in each etiology, and that the 'pathways in cancer' were selectively upregulated in the activated fibroblasts from MC4R-KO mice. The most upregulated gene in these pathways was fibroblast growth factor 9 (FGF9), which was induced by metabolic stress such as palmitate. FGF9 exerted anti-apoptotic and pro-migratory effects in fibroblasts and hepatoma cells in vitro and accelerated tumor growth in a subcutaneous xenograft model. This study reveals upregulation of cancer-associated gene expression in activated fibroblasts in NASH, which would contribute to the progression from NASH to HCC.
|
| 巻・号 |
9(1)
|
| ページ |
19601
|
| 公開日 |
2019-12-20
|
| DOI |
10.1038/s41598-019-56039-0
|
| PII |
10.1038/s41598-019-56039-0
|
| PMID |
31862949
|
| PMC |
PMC6925281
|
| MeSH |
Animals
Apoptosis
Carcinoma, Hepatocellular / metabolism
Cell Line, Tumor
Cell Movement
Cell Proliferation
Disease Progression
Fibroblast Growth Factor 9 / genetics
Fibroblasts / metabolism*
Gene Expression Profiling
Gene Expression Regulation, Neoplastic*
Humans
Liver / metabolism
Liver Cirrhosis / metabolism
Liver Neoplasms / metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Neoplasm Transplantation
Neoplasms / metabolism*
Non-alcoholic Fatty Liver Disease / metabolism*
Up-Regulation*
|
| IF |
3.998
|
| 引用数 |
1
|
| リソース情報 |
| ヒト・動物細胞 |
Hep G2 |
