中文摘要：

背景尽管肝的星形的房间(HSC ) 的迁居为肝的 fibrotic 反应是必要的，包含的详细机制糟糕被理解。这研究的目的是在导出血小板的生长检验 Rho GTPases (特别 RhoA ) 的角色 HSCs.Methods 的因素(PDGF )-BB-induced 移植主要老鼠 HSC 的迁居用 transwell Boyden 房间被评估，当细胞骨架变化被细胞内部的肌动朊和 vinculin 染色的 immunofluorescence 设想时。量的即时 PCR 和西方的弄污分析被用来在 HSC 以内检测 Rho GTPases (RhoA， Rac1 和 Cdc42 ) 的表示，他们的激活被谷胱甘肽 S-transferase 下拉试金决定。最后，改变的 PDGF-BB-induced 房间移植和细胞骨架上的 RhoA 的效果稳定地用 HSC-T6 房间被分析 transfected 与组成地活跃(CA， Q63L ) 或主导否定(DN， T19N ) RhoA 异种。数据用社会科学统计套装软体 16.0 软件被分析。学生的 t 测试被用来，变化(ANOVA ) 的单程的分析在多重 groups.Results 之中被使用快速的细胞骨架改变分析二个组之间的差别在 haptotactic 以后在主要老鼠 HSC 的活动性导致了重要增加(直接) 并且趋化性(间接) 由 PDGF-BB 的刺激。PDGF-BB 在总数和活跃 RhoA 蛋白质的层次引起了戏剧的举起。然而，包括 RhoA， Rac1 和 Cdc42，为 Rho GTPases 的 mRNA 的层次是未受影响的。而且， PDGF-BB 与 DN-RhoA 与 CA-RhoA 在 HSC-T6 房间 transfected，然而并非在 HSC-T6 transfected 导致了压力纤维和焦点的粘附的增加的形成。令人惊讶地， CA-RhoA-transfected 和 DN-RhoA-transfected HSC-T6 房间在缺席显示出减少的迁移的潜力或 PDGF-BB 的存在与 controls.Conclusions PDGF-BB 相比导致了在老鼠 HSC 改变的细胞骨架并且经由细胞内部的 RhoA 的规定支持了他们的迁居。RhoA 可以是在 PDGF-BB-induced HSC 移植的决定因素之一。

英文摘要：

Background Although the migration of hepatic stellate cells （HSCs） is essential for hepatic fibrotic response, the detailed mechanisms involved are poorly understood. The aim of this study was to examine the role of Rho GTPases （especially RhoA） in platelet-derived growth factor （PDGF）-BB-induced migration of HSCs. Methods The migration of primary rat HSCs was evaluated using transwell Boyden chamber, while cytoskeletal changes were visualized by immunofluorescence staining of intracellular actins and vinculin. Quantitative real-time PCR and Western blotting analysis were used to detect the expression of Rho GTPases （RhoA, Racl and Cdc42） within HSCs and their activation was determined by glutathione S-transferase pull-down assay. Finally, the effects of RhoA on PDGF-BB-induced cell migration and cytoskeletal remodeling were analyzed using HSC-T6 cells stably transfected with constitutively active （CA, Q63L） or dominant negative （DN, T19N） RhoA mutants. Data were analyzed using SPSS 16.0 software. Student＇s t test was used to analyze differences between two groups and one-way analysis of variance （ANOVA） was used among multiple groups. Results Rapid cytoskeletal remodeling led to a significant increase in the motility of primary rat HSCs after haptotactic （direct） and chemotactic （indirect） stimulation by PDGF-BB： PDGF-BB caused a dramatic elevation in the levels of both total and active RhoA protein. However, the levels of mRNA for Rho GTPases, including RhoA, Racl and Cdc42, were unaffected. Furthermore, PDGF-BB induced increased formation of stress fibers and focal adhesions in HSC-T6 cells transfected with CA-RhoA, but not in HSC-T6 transfected with DN-RhoA. Surprisingly, both CA- and DN-RhoA-transfected HSC-T6 cells showed decreased migratory potential in the absence or presence of PDGF-BB compared with controls. Conclusions PDGF-BB induced cytoskeletal remodeling in rat HSCs and promoted their migration via regulation of intracellular RhoA. RhoA may be one of the dete