MARCKS is a downstream effector in platelet-derived growth factor-induced cell motility in activated human hepatic stellate cells

被引：25

作者：

Rombouts, Krista ^{[1
,3
]}

Lottini, Benedetta ^{[1
,3
]}

Caligiuri, Alessandra ^{[1
,3
]}

Liotta, Francesco ^{[1
,3
]}

Mello, Tommaso ^{[2
,3
]}

Carloni, Vinicio ^{[1
,3
]}

Marra, Fabio ^{[1
,3
]}

Pinzani, Massimo ^{[1
,3
]}

机构：

[1] Univ Florence, Dept Internal Med, I-50134 Florence, Italy

[2] Univ Florence, Dept Clin Pathophysiol, I-50134 Florence, Italy

[3] Univ Florence, Ctr Res Transfer & High Educ DENOThe, I-50134 Florence, Italy

来源：

EXPERIMENTAL CELL RESEARCH | 2008年 / 314卷 / 07期

关键词：

MARCKS; protein kinase C; chemotaxis; human hepatic stellate cells; liver fibrosis; PDGF; RNAi;

D O I：

10.1016/j.yexcr.2008.01.029

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Myristoylated alanine-rich protein kinase c substrate (MARCKS) has been suggested to be implicated in cell adhesion, secretion, motility and mitogenesis through regulation of the actin cytoskeletal structure. In the present study, a possible link between MARCKS and the platelet-derived growth factor (PDGF) signaling pathway was investigated in activated human hepatic stellate cells (hHSC), critical regulators of hepatic fibrogenesis. PDGF-BB stimulation resulted in a bi-directional movement of MARCKS that coincided with the phosphorylation of MARCKS and the activation of both PKC epsilon and PKC alpha. Biochemical inhibition of PKC kinase activity and small interfering RNA (siRNA) against PKC epsilon demonstrated that PKC epsilon is indispensable for PDGF-BB-induced MARCKS phosphorylation and cell migration. Immunoprecipitation studies revealed an association between MARCKS and the PDGF beta-receptor, while the PDGF beta-receptor and PKC alpha associated with focal adhesion kinase (FAK). Transient transfection with MARCKS DNA plasmid remarkably reduced PDGF-BB stimulated cell motility. in contrast, siRNA against MARCKS increased cell migration in RNAi treated cells in comparison to the scrambled control cells. In conclusion, the present study indicates that MARCKS play a major key role in PDGF-BB-induced chemotaxis in activated hHSC. (C) 2008 Elsevier Inc. All rights reserved.

引用

页码：1444 / 1454

页数：11

共 45 条

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