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Antagonistic effect of C19 on migration of vascular smooth muscle cells and intimal hyperplasia induced by chemokine-like factor 1

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Abstract

A chemokine-like factor 1 (CKLF1) is a recently discovered chemokine with broad-spectrum biological functions in inflammation and autoimmune diseases. C19 as a CKLF1’s C-terminal peptide has been reported to exert inhibitory effects in a variety of diseases. However, the roles of CKLF1 and C19 on vascular smooth muscle cell (VSMC) migration and neointima formation still remain elusive. The effects of CKLF1 and C19 on VSMC migration and neointimal formation were investigated in cultured VSMCs and balloon-injured rat carotid arteries based on techniques including adenovirus-induced CKLF1 overexpression, gel based perivascular administration of C19, Boyden chamber, scratch-wound assay, real-time PCR, western blot and immunohistochemical analysis. CKLF1 was noticed to accumulate preferentially in neointima after the injury and colocalize with VSMCs. Luminal delivery of CKLF1 adenovirus to arteries exacerbated intimal thickening while perivascular administration of C19 to injured arteries attenuated this problem. In cultured primary VSMCs, CKLF1 overexpression up-regulated VSMC migration, which was down-regulated by C19. These data suggest that CKLF1 has a pivotal role in intimal hyperplasia by mediating VSMC migration. C19 was demonstrated to inhibit CKLF1-mediatated chemotaxis and restenosis. Thus further studies on C19 may provide a new treatment perspective for atherosclerosis and post-angioplasty restenosis.

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Acknowledgments

This work was supported by the China Postdoctoral Science Foundation (Grant No. 201150M1532). We thank Prof. Wenling Han and Ying Wang from the Laboratory of Medical Immunology, School of Basic Medical Science, Peking University, for the generous gifts of the recombinant adenovirus carrying CKLF1, antibodies for CKLF1 and C19.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Vascular Surgery, Clinical Division of Surgery, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing, 100853, China

    Tao Zhang, Feng Chen, Jiang Xiong, Xin Jia & Wei Guo

  2. Department of Central Laboratory, Peking University People’s Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China

    Zhengguo Qiao

  3. Department of Vascular Surgery, Peking University People’s Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China

    Xiaoming Zhang & Chenyang Shen

  4. State Key Laboratory of Transducer Technology, Institute of Electronics, Chinese Academy of Sciences, No. 19 North Fourth Ring Road, Haidian District, Beijing, 100190, China

    Jian Chen

Authors
  1. Tao Zhang
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  2. Zhengguo Qiao
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  3. Feng Chen
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  4. Xiaoming Zhang
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  5. Jiang Xiong
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  6. Xin Jia
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  7. Jian Chen
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  8. Chenyang Shen
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  9. Wei Guo
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Corresponding authors

Correspondence to Chenyang Shen or Wei Guo.

Additional information

Tao Zhang, Zhengguo Qiao, and Feng Chen contributed equally to the manuscript.

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11033_2012_2309_MOESM1_ESM.tif

Supplementary Fig. 1 Representative western blots of CKLF1 protein in carotid arteries on day 7 after injury, based on Ad-GFP trasnfection and Ad-CKLF1 transfection, respectively (5 × 108 pfu). Values are mean ± SEM. n = 3 each group. *P < 0.05 versus Ad-GFP group

11033_2012_2309_MOESM2_ESM.tif

Supplementary Fig. 2 (A) Immunofluorescent microscopic pictures of transfected VSMCs with Ad-GFP at different doses (50, 100, 200 and 300 mois, scale bar = 40 μm). Since 200 mois infection lead to 80–90 % cells with green fluorescent protein expression after 2 days and lasted at least for 2 weeks without signs of cell damage, this optimal dose was used in subsequent studies. Figure 2(B) CKLF1 mRNA levels of VSMCs transfected with Ad-GFP or Ad-CKLF1 (50 MOI, 100 MOI, 200 MOI and 300 MOI). Values are mean ± SEM. n = 3 per group. *P < 0.05 versus Ad-GFP group. (C)A microscopic picture of VSMCs (200 mois infection) stained with specific anti-CKLF1 antibody as an indicator of CKLF1 expression in the protein level (magnification ×100)

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Zhang, T., Qiao, Z., Chen, F. et al. Antagonistic effect of C19 on migration of vascular smooth muscle cells and intimal hyperplasia induced by chemokine-like factor 1. Mol Biol Rep 40, 2939–2946 (2013). https://doi.org/10.1007/s11033-012-2309-1

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  • DOI: https://doi.org/10.1007/s11033-012-2309-1

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