Recombinant SjP40 protein enhances p27 promoter expression in hepatic stellate cells via an E2F1-dependent mechanism
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Yinong Duan1,*, Lei Lyu1,*, Dandan Zhu1,*, Jianxin Wang2, Jinling Chen1, Liuting Chen1, Chunzhao Yang1 and Xiaolei Sun1
1Department of Pathogen Biology, School of Medicine, Nantong University, Nantong 226001, Jiangsu, People’s Republic of China
2Laboratory Medicine Center, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, People’s Republic of China
*These authors contributed equally to this work
Yinong Duan, email: [email protected]
Keywords: liver fibrosis, P40, p27, E2F1, Schistosoma japonicum
Received: December 20, 2016 Accepted: April 06, 2017 Published: April 19, 2017
The p27 protein plays a critical role in cell cycle arrest. Our previous studies have demonstrated that recombinant P40 protein from Schistosoma japonicum (rSjP40) could induce G1 phase arrest of cell cycle. We, therefore, attempted to observe the effect of rSjP40 on p27 promoter activity in LX-2 cells and to explore its potential mechanisms in this study. Using both Western blot and dual-luciferase reporter assay, we demonstrated that rSjP40 could enhance the expression of p27 in LX-2 cells. Results obtained using truncated fragments of p27 promoter showed that rSjP40 increased p27 promoter activity in LX-2 cells, mainly via some transcription factors that bind to the -1740/-873 region of p27 promoter. Further studies confirmed that the enhancement of p27 promoter activity induced by rSjP40 was related to E2F1 in LX-2 cells. Transfection of siRNA of E2F1 could also restore the effect of rSjP40 on expression of p27 and partially on α-SMA. Therefore, our study provided further insights into the mechanism by which rSjP40 induces LX-2 cell cycle arrest at G1 phase and inhibits HSC activation. Our results provide basis for future study of the blocking effect of rSjP40 in liver fibrosis.
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