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.

Static magnetic fields enhance dental pulp stem cell proliferation by activating the p38 mitogen-activated protein kinase pathway as its putative mechanism

“…Actin is present in the cytoplasm as a monomeric G‐actin or as a reversibly assembled polymeric F‐actin filament. G‐actin molecules polymerize into F‐actin when their concentration increases (Cui et al ., ). This result represents that cytoskeleton was in a state of being remodelled, in which actin monomeric G‐actin was highly increased in the cytoplasm.…”

In vitro structure-toxicity relationship of chalcones in human hepatic stellate cells

“…In vivo, an activation of hepatic stellate cells can finally lead to the disease state of hepatic fibrosis. It was previously reported that F-actin cytoskeletal reorganization is an essential step in the activation of hepatic stellate cells (Cui et al, 2014). The cell model might therefore also be suitable to determine if and how substances alter the activation state and thereby a disease progression.…”

Role of liver ICAM-1 in metastasis

“…HSCs respond to VEGF produced by tumor-activated cells and migrate to the sites of angiogenesis (109). The p38 mitogen-activated protein kinase (MAPK) pathway has been recently proposed as a mediator of endothelial cell activation, cytoskeletal reorganization and migration of HSCs (110,111). Interestingly, ICAM-1 activation has been shown to stimulate the p38 MAPK pathway in endothelial cells, astrocytes and renal fibroblasts (112)(113)(114).…”