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TGF-β1 enhances SDF-1-induced migration and tube formation of choroid-retinal endothelial cells by up-regulating CXCR4 and CXCR7 expression

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Abstract

Stromal derived factor (SDF)-1 has been confirmed to regulate angiogenesis in choroidal neovascularization formation via its two receptors, CXC chemokine receptors 4 (CXCR4) and 7 (CXCR7). Previous studies found that there is cross-talk between the transforming growth factor beta (TGF-β) and SDF-1 pathways in some types of immune or tumor cells, but much less is known about this interaction in endothelial cells. This study investigated the effects of TGF-β1 on CXCR4 and CXCR7 expression as well as SDF-1-induced migration and tube formation in choroid-retinal endothelial (RF/6A) cells. RF/6A cells were treated with recombinant TGF-β1 at various concentrations and time points. Real-time PCR and Western blotting were used to examine the mRNA and protein levels of CXCR4 and CXCR7. In addition, transwell migration and Matrigel tube formation analyses were performed to investigate the role of TGF-β1 pretreatment in SDF-1-induced RF/6A cell migration and tube formation. Our results showed that treatment with recombinant human TGF-β1 enhanced the CXCR4 and CXCR7 levels in time- and dose-dependent manners. The increased CXCR4 and CXCR7 expression resulted in increased SDF-1-induced RF/6A cell migration and tube formation. In addition, the transcriptional regulation of CXCR4 and CXCR7 by TGF-β1 was found to be mediated by phosphorylation of the extracellular signal-related kinase1/2 pathway. Altogether, these results demonstrate that a cross-talk exists between the TGF-β1 and SDF-1 pathways in choroid-retinal endothelial cells, reflecting a novel molecular mechanism that explains the pro-angiogenic effects of TGF-β1 and possibly provides new perspectives for the treatment of CNV-associated diseases.

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Acknowledgments

This study was supported by grants from the National Nature Science Foundation of China (No. 81470637, http://www.nsfc.gov.cn) and the Open Fund of the Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education (No. KLCCI2014-1). The authors thank Dr. Mohammad Javed Ali for his help on the manuscript.

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Authors and Affiliations

  1. Department of Ophthalmology, Zhongshan Hospital, Fudan University, 180# Fenglin Road, Shanghai, 200032, People’s Republic of China

    Yi-fan Feng, Fei Yuan & Hua Guo

  2. Liver Cancer Institute and Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, People’s Republic of China

    Wei-zhong Wu

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  1. Yi-fan Feng
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  2. Fei Yuan
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Correspondence to Fei Yuan.

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Feng, Yf., Yuan, F., Guo, H. et al. TGF-β1 enhances SDF-1-induced migration and tube formation of choroid-retinal endothelial cells by up-regulating CXCR4 and CXCR7 expression. Mol Cell Biochem 397, 131–138 (2014). https://doi.org/10.1007/s11010-014-2180-6

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  • DOI: https://doi.org/10.1007/s11010-014-2180-6

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