Secondary Unconjugated Bile Acids Induce Hepatic Stellate Cell Activation

被引:19
|
作者
Saga, Kunihiro [1 ]
Iwashita, Yukio [1 ]
Hidano, Shinya [2 ]
Aso, Yuiko [1 ]
Isaka, Kenji [1 ]
Kido, Yasutoshi [3 ]
Tada, Kazuhiro [1 ]
Takayama, Hiroomi [1 ]
Masuda, Takashi [1 ]
Hirashita, Teijiro [1 ]
Endo, Yuichi [1 ]
Ohta, Masayuki [1 ]
Kobayashi, Takashi [2 ]
Inomata, Masafumi [1 ]
机构
[1] Oita Univ, Fac Med, Dept Gastroenterol & Pediat Surg, 1-1 Idaigaoka, Hasama, Oita 8795593, Japan
[2] Oita Univ, Fac Med, Dept Infect Dis Control, 1-1 Idaigaoka, Hasama, Oita 8795593, Japan
[3] Oita Univ, Fac Med, Dept Environm & Prevent Med, 1-1 Idaigaoka, Hasama, Oita 8795593, Japan
基金
日本学术振兴会;
关键词
hepatic stellate cell; secondary unconjugated bile acid; DNA microarray; tumor necrosis factor signaling pathway; NF-KAPPA-B; LIVER-CANCER; QUANTITATIVE ESTIMATION; RECEPTOR FXR; TNF-ALPHA; INFLAMMATION; FIBROSIS; OBESITY; DIFFERENTIATION; BIOLOGY;
D O I
10.3390/ijms19103043
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Hepatic stellate cells (HSCs) are key players in liver fibrosis, cellular senescence, and hepatic carcinogenesis. Bile acids (BAs) are involved in the activation of HSCs, but the detailed mechanism of this process remains unclear. We conducted a comprehensive DNA microarray study of the human HSC line LX-2 treated with deoxycholic acid (DCA), a secondary unconjugated BA. Additionally, LX-2 cells were exposed to nine BAs and studied using immunofluorescence staining, enzyme-linked immunosorbent assay, and flow cytometry to examine the mechanisms of HSC activation. We focused on the tumor necrosis factor (TNF) pathway and revealed upregulation of genes related to nuclear factor kappa B (NF-B) signaling and senescence-associated secretory phenotype factors. -Smooth muscle actin (-SMA) was highly expressed in cells treated with secondary unconjugated BAs, including DCA, and a morphological change associated with radial extension of subendothelial protrusion was observed. Interleukin-6 level in culture supernatant was significantly higher in cells treated with secondary unconjugated BAs. Flow cytometry showed that the proportion of cells highly expressing -SMA was significantly increased in HSCs cultured with secondary unconjugated BAs. We demonstrated that secondary unconjugated BAs induced the activation of human HSCs.
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页数:18
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