[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.

Conclusion: 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.