Egg antigen p40 of Schistosoma japonicum promotes senescence in activated hepatic stellate cells via SKP2/P27 signaling pathway.
Schistosomiasis is characterized by egg deposition, granulomatous inflammatory reaction and then subsequent hepatic fibrosis formation. Activated HSCs are regarded as the main effector cells in the progression of liver fibrosis and induction of senescence in hepatic stellate cells (HSCs) is vital to the reversion of hepatic fibrosis. Our previous work has showed that S. japonicum egg antigen p40 (Sjp40) could promote HSCs senescence via a STAT3/p53/p21 mechanism. In this paper, the major aim was to explore whether there are other signaling pathways in the process of Sjp40-induced HSCs aging and the underlying effect of SKP2/P27 signal pathway in this procedure. We observed the Sjp40-induced decrease of α-SMA and the senescence of LX-2 cells, and Sjp40 could upregulate P27 and downregulate the protein level of SKP2. The senescence induced by Sjp40 might be reversed in LX-2 cells that treated with P27-specific siRNA or with SKP2-special over-expression plasmid. In addition, we also demonstrated that the decreased expression of P-Rb and α-SMA induced by Sjp40 were partly restored by SKP2-overexpression. These data suggest that Sjp40 might inhibit HSCs activation by promoting cellular senescence via SKP2/P27 signaling pathway, which put forward novel mechanism in the treatment of liver fibrosis.
Department of Pathogen Biology, School of Medicine, Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.|Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, People's Republic of China.
Tianhua
T
Xu
Department of Pathogen Biology, School of Medicine, Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.
Jinling
J
Chen
Department of Pathogen Biology, School of Medicine, Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.
Dandan
D
Zhu
Department of Pathogen Biology, School of Medicine, Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.
Liuting
L
Chen
Laboratory Medicine Center, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.
Jianxin
J
Wang
Department of Pathogen Biology, School of Medicine, Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.
Xiaolei
X
Sun
Department of Pathogen Biology, School of Medicine, Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.
Bin
B
Hu
Department of Pathogen Biology, School of Medicine, Nantong University, Nantong, 226001, Jiangsu, People's Republic of China. yinongduan@aliyun.com.
Yinong
0000-0001-5824-5762
Y
Duan
D000818:Animals; D000947:Antigens, Helminth / Q000378:metabolism*; D002460:Cell Line; D016922:Cellular Senescence / Q000187:drug effects*; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D044786:S-Phase Kinase-Associated Proteins / Q000378:metabolism*; D012549:Schistosoma japonicum / Q000737:chemistry*; D015398:Signal Transduction; D015053:Zygote / Q000737:chemistry
D000947:Antigens, Helminth; D018809:Proliferating Cell Nuclear Antigen; D044786:S-Phase Kinase-Associated Proteins; C413374:p27 antigen