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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URL: https://zhptwkxwx.cma-cmc.com.cn/EN/10.3877/cma.j.issn.1674-0793.2014.05.005

https://zhptwkxwx.cma-cmc.com.cn/EN/Y2014/V08/I05/353

Figures/Tables 6

References 10

[1]	Xiao Y,Wang J,Chen Y, et al. Up-regulation of miR-200b in biliary atresia patients accelerates proliferation and migration of hepatic stellate cells by activating PI3K/Akt signaling[J]. Cell Signal, 2014, 26(5): 925-932.
[2]	Tang LX,He RH,Yang G, et al. Asiatic acid inhibits liver fibrosis by blocking TGF-beta/Smad signaling in vivo and in vitro[J]. PLoS One, 2012, 7(2): e31350.
[3]	Dechêne A,Sowa JP,Gieseler RK, et al. Acute liver failure is associated with elevated liver stiffness and hepatic stellate cell activation[J]. Hepatology, 2010, 52(3): 1008-1016.
[4]	Li L,Wang JY,Yang CQ, et al. Effect of RhoA on transforming growth factor β1-induced rat hepatic stellate cell migration[J]. Liver Int, 2012, 32(7): 1093-1102.
[5]	Chen PS,Wang MY,Wu SN, et al. CTGF enhances the motility of breast cancer cells via an integrin-alphavbeta3-ERK1/2-dependent S100A4-upregulated pathway[J]. J Cell Sci, 2007, 120(Pt 12): 2053-2065.
[6]	Pan MR,Hung WC. Nonsteroidal anti-inflammatory drugs inhibit matrix metalloproteinase-2 via suppression of the ERK/Sp1-mediated transcription[J]. J Biol Chem, 2002, 277(36): 32775-32780.
[7]	Kurata H,Thant AA,Matsuo S, et al. Constitutive activation of MAP kinase kinase (MEK1) is critical and sufficient for the activation of MMP-2[J]. Exp Cell Res, 2000, 254(1): 180-188.
[8]	Vivanco I,Sawyers CL. The phosphatidylinositol 3-Kinase AKT pathway in human cancer[J]. Nat Rev Cancer, 2002, 2(7): 489-501.
[9]	Radhakrishnan SS,Blalock TD,Robinson PM, et al. Effect of connective tissue growth factor on protein kinase expression and activity in human corneal fibroblasts[J]. Invest Ophthalmol Vis Sci, 2012, 53(13): 8076-85.
[10]	Uyama N,Iimuro Y,Kawada N, et al. Fascin, a novel marker of human hepatic stellate cells, may regulate their proliferation, migration, and collagen gene expression through the FAK-PI3K-Akt pathway[J]. Lab Invest, 2012, 92(1): 57-71．

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