CTGF promoting migration and MMP-2 expression via ERK1/2 and PI3K pathway in rat hepatic stellate cells

doi:10.3877/cma.j.issn.1674-0793.2014.05.005

Abstract

Abstract:

Objective

To identify the role of connective tissue growth factor (CTGF) in hepatic stellate cell (HSC) migration and its effects on gelatinase matrix metalloproteinase-2 (MMP-2) expression and activation.

Methods

The expression of MMP-2 was assessed by RT-PCR and Western blotting analyses. MMP-2 activity was evaluated by zymography. ERK1/2 and Akt phosphorylation were determined by Western blotting analysis. HSC migration was performed using Transwell cell culture chambers.

Results

The expression of MMP-2 mRNA and protein in HSCs were substantially increased by CTGF treatment in a dose-dependent manner. In addition, CTGF could promote HSC migration, and the addition of MMP-2-specific inhibitor impaired this phenomenon. To study the intracellular signaling pathways involved in CTGF-induced MMP-2 expression, we evaluated the effects of different kinase inhibitors. The inhibitors of extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphatidyl inositol 3-kinase (PI3K) abrogated CTGF-elicited MMP-2 upregulation and significantly reduced CTGF-induced invasiveness of HSC.

Conclusion

MMP-2 plays an important role in the invasive effects of CTGF on HSC. ERK1/2 and PI3K are the main signals involved in CTFG-mediated MMP-2 expression.

Key words: Matrix metalloproteinase, Hepatic stellate cell, Migration, Connective tissue growth factor

Maochuan Zhen, Pingguo Liu, Yilin Zhao, Shaofeng Wu, Keke Yu, Zhenyu Yin. CTGF promoting migration and MMP-2 expression via ERK1/2 and PI3K pathway in rat hepatic stellate cells[J]. Chinese Archives of General Surgery(Electronic Edition), 2014, 08(05): 353-358.

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Figures/Tables 6

References 10

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