[Regulatory effects of RhoGTPase on transition of liver sinusoidal capillarization: experiment with mice of schistosomal hepatic fibrosis].
OBJECTIVE
To investigate the regulatory effects of RhoGTPase on the transition of liver sinusoidal endothelial cells and the potential mechanism thereof on the sinusoidal capillarization in schistosomal hepatic fibrosis.


METHODS
Eight-eight mice underwent abdominal infection of schistosomal cercaria so as to establish liver fibrosis models. 13 weeks later the mice were divided into 5 groups: Group A (normal control group, n = 10), Group B (group of schistosomiasis, n = 24), Group C (anti-schistosoma control group, treated with biltricide), Group D (group of schistosomiasis + hydroxyfasudil, treated with hydroxyfasudil since the week 14, n = 18), and Group E (biltricide + hydroxyfasudil, treated with biltricide since week 13 and added with hydroxyfasudil since week 14, n = 18). The mice in Group A and 6 mice of Group B were killed in week 13, and 6 mice of Groups B, C, D, and E were killed in weeks 16, 19, and 21 each. The livers were taken out to undergo electron microcopy. Immunohistochemistry was used to detect the expression of p-moesin, connective tissue growth factor (CTGF), RhoA, collagen IV (Col IV), and laminin (LN) protein expressions were assessed by Western blotting, and RT-PCR was used to detect the mRNA expression of CTGF, RhoA, and ROCK II.


RESULTS
Compared with Group A, the mRNA levels of RhoA, ROCK II, and CTGF were significantly increased (all P < 0.05) and the protein expression levels of p-moesin, CTGF, RhoA, Col IV, and LN were significantly increased (all P < 0.05) in Group B. After intervention with biltricide and/or hydroxyfasudil, the CTGF mRNA expression was significantly decreased (P < 0.05) in Group E in week 16 and the protein expression levels of CTGF, Col IV, and LN were decreased (all P < 0.05) compared with other groups, and the expression of p-moesin of Group E was significantly lower than that of Group D (P < 0.05). Electron microcopy showed that the liver sinusoids of the mice in Group E was significantly better compared with the other groups, and there was no significant difference between Groups B and D.


CONCLUSIONS
An upregulation of RhoGTPase that contributes to increased CTGF expression and phosphorylation of moesin may induce a transition of liver sinusoidal endothelial cells in schistosomiasis.
Zhang
Ai-long
AL
Department of General Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, China.
Yang
Zhen
Z
Xiao
Liang
L
Li
Dong-jian
DJ
Niu
Li-wen
LW
D000818:Animals; D002196:Capillaries / Q000378:metabolism / Q000473:pathology; D004727:Endothelium / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D006503:Hepatic Veins / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D012554:Schistosomiasis japonica / Q000150:complications; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*