title: F‑actin cytoskeleton reorganization is associated with hepatic stellate cell activation.
abstract: The activation of hepatic stellate cells (HSCs) is involved in the development of hepatic fibrosis. Previous studies have indicated that the acquisition of certain properties by activated HSCs is highly dependent on the reorganization of the actin cytoskeleton. However, direct evidence showing that the reorganization of the actin cytoskeleton is responsible for HSC activation is lacking. The aim of the present study was to investigate the role of cytoskeletal reorganization during HSC activation and to clarify the underlying mechanism. HSC-T6 cells were treated either with the F-actin stabilizer jasplakinolide (Jas) or the depolymerizer cytochalasin D (Cyto D). The actin cytoskeleton was evaluated via assessment of stress fiber formation. Furthermore, the activation properties of HSCs, including proliferation, adhesion, migration and the expression of α-smooth muscle actin (α-SMA) and collagen 1, were investigated in vitro. The results showed that Jas and Cyto D affected the actin distribution in HSC-T6 cells. Treatment with Jas resulted in thick actin bundles and a patchy appearance in the cytoplasm in HSC-T6 cells. In parallel, polymerization of actin microfilaments induced by Jas upregulated the expression of α-SMA and collagen 1, and also enhanced the migration and adhesion properties of HSC-T6 cells. Furthermore, the activation of HSC-T6 cells induced by the reorganization of the actin cytoskeleton was associated with the p38 mitogen-activated protein kinase (p38 MAPK) pathway. In conclusion, the present study suggests that the reorganization of the F-actin cytoskeleton is associated with HSC activation and that the p38 MAPK pathway is involved in this process. The inhibition of F-actin reorganization may thus be a potential key factor or molecular target for the control of liver fibrosis or cirrhosis.
authors.affiliation: Medical Research Center, Weifang Medical University, Weifang, Shandong 261053, P.R. China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Cui
authors.affiliation: Medical Research Center, Weifang Medical University, Weifang, Shandong 261053, P.R. China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Medical Research Center, Weifang Medical University, Weifang, Shandong 261053, P.R. China.
authors.forename: Qingling
authors.initials: Q
authors.lastname: Yin
authors.affiliation: Medical Research Center, Weifang Medical University, Weifang, Shandong 261053, P.R. China.
authors.forename: Aixia
authors.initials: A
authors.lastname: Meng
authors.affiliation: Medical Research Center, Weifang Medical University, Weifang, Shandong 261053, P.R. China.
authors.forename: Shaojuan
authors.initials: S
authors.lastname: Su
authors.affiliation: Medical Research Center, Weifang Medical University, Weifang, Shandong 261053, P.R. China.
authors.forename: Xu
authors.initials: X
authors.lastname: Jing
authors.affiliation: Medical Research Center, Weifang Medical University, Weifang, Shandong 261053, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: Medical Research Center, Weifang Medical University, Weifang, Shandong 261053, P.R. China.
authors.forename: Xiumei
authors.initials: X
authors.lastname: Guan
authors.affiliation: Medical Research Center, Weifang Medical University, Weifang, Shandong 261053, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Medical Research Center, Weifang Medical University, Weifang, Shandong 261053, P.R. China.
authors.forename: Shunmei
authors.initials: S
authors.lastname: Liu
authors.affiliation: Medical Research Center, Weifang Medical University, Weifang, Shandong 261053, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Cheng
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D015638:Cytochalasin D / Q000494:pharmacology; D047630:Depsipeptides / Q000494:pharmacology; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000199:Actins; D047630:Depsipeptides; C057531:jasplakinolide; D015638:Cytochalasin D; D048051:p38 Mitogen-Activated Protein Kinases