title: Effect of Kruppel-like factor 4 on Notch pathway in hepatic stellate cells.
abstract: The relationship between Kruppel-like factor 4 (KLF4) and the Notch pathway was determined to investigate the effect of KLF4 on the activation of hepatic stellate cells and underlying mechanisms. Fifty SPF BALB/c mice were randomly divided into two groups. A liver fibrosis model was established in 25 mice as the experimental group, and the remaining 25 mice served as controls. On the day 0, 7, 14, and 35, liver tissues were removed for immunofluorescent detection. The Notch pathway inhibitor DAPT was added to the primary original hepatic stellate cells, and KLF4 and Notch-associated factor expression was detected by qRT-PCR. Additionally, the hepatic stellate cell line LX-2 was used to establish control and experimental groups, and was cultured in vitro. LX-2 cells in the experimental groups were treated with DAPT and the Notch activator transforming growth factor-beta 1 separately, whereas those in the control group were given isotonic culture medium. After 48 h, KLF4 expression was examined by Western blotting. After transient transfection of LX-2 cells to increase KLF4, the expression of Notch factor was examined. Immunofluorescence analysis showed that, with the aggravation of liver fibrosis, the absorbance (A) values of KLF4 were decreased (day 0: 980.73±153.19; day 7: 1087.99±230.23; day 14: 390.95±93.56; day 35: 245.99±87.34). The expression of Notch pathway- related factors (Notch-1, Notch-2, and Jagged-1) in the hepatic stellate cell membrane was negatively correlated to KLF4 expression. With the increase of KLF4 expression, Notch-2 (0.73±0.13) and Jagged-1 (0.43±0.12) expression decreased, whereas Notch-1 level was not detectable. When the Notch pathway was inhibited, KLF4 levels generally increased (18.12±1.31). Our results indicate that KLF4 expression is negatively correlated to the Notch pathway in hepatic stellate cells, which may provide a reference for the treatment of hepatic fibrosis.
authors.affiliation: Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong Univerfsity of Science and Technology, Wuhan, 430022, China.
authors.forename: Yin-Kai
authors.initials: YK
authors.lastname: Xue
authors.affiliation: Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong Univerfsity of Science and Technology, Wuhan, 430022, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Tan
authors.affiliation: Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong Univerfsity of Science and Technology, Wuhan, 430022, China.
authors.forename: Dong-Wei
authors.initials: DW
authors.lastname: Dou
authors.affiliation: Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong Univerfsity of Science and Technology, Wuhan, 430022, China.
authors.forename: Ding
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong Univerfsity of Science and Technology, Wuhan, 430022, China.
authors.forename: Lu-Jia
authors.initials: LJ
authors.lastname: Chen
authors.affiliation: Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong Univerfsity of Science and Technology, Wuhan, 430022, China.
authors.forename: Huan-Ping
authors.initials: HP
authors.lastname: Ren
authors.affiliation: Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong Univerfsity of Science and Technology, Wuhan, 430022, China.
authors.forename: Li-Bo
authors.initials: LB
authors.lastname: Chen
authors.affiliation: Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong Univerfsity of Science and Technology, Wuhan, 430022, China. gaoleilei2008@aliyun.com.
authors.forename: Xin-Gao
authors.initials: XG
authors.lastname: Xiong
authors.affiliation: Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong Univerfsity of Science and Technology, Wuhan, 430022, China. zhenghai999@126.com.
authors.forename: Hai
authors.initials: H
authors.lastname: Zheng
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D055166:Hepatic Stellate Cells / Q000378:metabolism*; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D051880:Receptors, Notch; D053773:Transforming Growth Factor beta1
keywords: KLF4; Notch; hepatic fibrosis; hepatic stellate cells