Enhanced Wnt Signalling in Hepatocytes is Associated with Schistosoma japonicum Infection and Contributes to Liver Fibrosis.
Liver fibrosis is the most serious pathology caused by Schistosoma japonicum infection, which arises when schistosome eggs are deposited in the liver. Eosinophils, macrophages and hepatic stellate cells (HSCs) have been identified as major cellular contributors to the development of granulomas and fibrosis, but little is known about the effects of hepatocytes on granuloma formation. Here, we found that the levels of Wnt signalling-related molecules, transforming growth factor β (TGF-β) and connective tissue growth factor (CTGF) in hepatocytes were markedly elevated after S. japonicum infection. Liver fibrosis was exacerbated when exogenous Wnt3a was introduced, but was alleviated when Wnt signalling was suppressed by DKK1, accompanied by the reduced expression of TGF-β and CTGF in hepatocytes. These results indicate that the hepatocytic expression of TGF-β and CTGF is mediated by Wnt signalling. Additionally, the hepatocytes isolated from infected mice promoted the activation of primary HSCs in vitro, however, this effect was not observed when hepatocytes from DKK1 treated S. japonicum-infected mice was employed in the co-culture system. Our findings identify a novel pro-fibrogenic role of hepatocytes in schistosomiasis-induced liver fibrosis that is dependent on Wnt signalling, which may serve as a potential target for ameliorating hepatic fibrosis caused by helminths.
Department of Parasitology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
Qi
Q
Wang
Department of Parasitology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
Xin
X
Chou
Department of Parasitology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
Fei
F
Guan
Department of Parasitology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
Zhengming
Z
Fang
Department of Parasitology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
Shengjun
S
Lu
Department of Parasitology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
Jiahui
J
Lei
Department of Parasitology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
Yonglong
Y
Li
Department of Parasitology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China. liu_wq2002cn@hotmail.com.
Wenqi
W
Liu
D000818:Animals; D055513:Connective Tissue Growth Factor / Q000032:analysis*; D022781:Hepatocytes / Q000469:parasitology*; D008103:Liver Cirrhosis / Q000473:pathology*; D008807:Mice, Inbred BALB C; D012549:Schistosoma japonicum / Q000254:growth & development*; D012554:Schistosomiasis japonica / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000032:analysis*; D060449:Wnt Signaling Pathway; D060509:Wnt3A Protein / Q000378:metabolism*
C526318:CCN2 protein, mouse; D016212:Transforming Growth Factor beta; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse; D055513:Connective Tissue Growth Factor