Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=28331224
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Enhanced Wnt Signalling in Hepatocytes is Associated with Schistosoma japonicum
Infection and Contributes to Liver Fibrosis
#MMPMID28331224
Wang Q
; Chou X
; Guan F
; Fang Z
; Lu S
; Lei J
; Li Y
; Liu W
Sci Rep
2017[Mar]; 7
(1
): 230
PMID28331224
show ga
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 ? (TGF-?) 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-? and CTGF in
hepatocytes. These results indicate that the hepatocytic expression of TGF-? 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.
|*Wnt Signaling Pathway
[MESH]
|Animals
[MESH]
|Connective Tissue Growth Factor/*analysis
[MESH]
|Hepatocytes/*parasitology
[MESH]
|Liver Cirrhosis/*pathology
[MESH]
|Mice, Inbred BALB C
[MESH]
|Schistosoma japonicum/*growth & development
[MESH]
free
free
free
