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C1ql1/Ctrp14 and C1ql4/Ctrp11 promote angiogenesis of endothelial cells through activation of ERK1/2 signal pathway

Molecular and Cellular Biochemistry volume 424, pages 57–67 (2017)Cite this article

Abstract

C1ql-like (C1QL)-1 and -4 proteins are encoded by homologous genes that are highly expressed in brain and adipose tissues. However, functional properties of C1QL proteins outside of the brain and adipocytes remain unknown. Here, we report that the globular domain of C1ql1/Ctrp14 and C1ql4/Ctrp11 proteins directly stimulate the angiogenesis of endothelial cells. In this study, soluble C1ql1/CTRP14 and C1ql4/Ctrp11 proteins, produced in prokaryote expression system, are co-cultured with human umbilical vein endothelium cells (HUVECs), which phenotype is identified with von Willebrand factor antibody. C1ql1/Ctrp14 and C1ql4/Ctrp11 promote the migration and capillary tube formation of HUVECs in a dose-dependent manner. During this process, phosphorylation of c-Raf, MEK1/2, ERK1/2, and p90RSK are activated by C1ql1/Ctrp14 and C1ql4/Ctrp11. MEK1/2 inhibitor, U0126, blocks C1ql1/Ctrp14-, and C1ql4/Ctrp11-induced capillary tube formation and cell migration. Moreover, the immunoreactivity of the receptor of C1QL1-C1QL4, brain-specific angiogenesis inhibitor 3 (BAI3), is detected in HUVECs, suggesting that BAI3 may mediate C1QL1/CTRP14- and C1QL4/CTRP11-induced angiogenesis. Meanwhile, C1ql1/Ctrp14 and C1ql4/Ctrp11 exposure also causes a stimulatory response of angiogenesis in chick yolk sac membrane. These data demonstrate that C1ql1/Ctrp14 and C1ql4/Ctrp11 stimulate the new blood vessel growth by activation of ERK1/2 signal pathway. The proangiogenic activity of C1ql1/Ctrp14 and C1ql4/Ctrp11 provides novel insights into the new opportunities for therapeutic intervention by targeting C1QLs in tumorigenesis, tissue regeneration, and recovery of ischemic heart disease.

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Acknowledgments

This work was supported by the Project 30900232 of the National Natural Science Foundation, Project 200801259 of the China Postdoctoral Science Foundation, Project sybzzxm201033 of Guangdong Province Excellent Doctoral Thesis Foundation, and Project 2013J2200026 of the Science &Technology Star of Pearl River, Guangzhou City.

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Authors and Affiliations

  1. Key Laboratory for Regenerative Medicine (JNU-CUHK) Ministry of Education, Jinan University, Guangzhou, China

    Fang Liu, Anni Tan, Renhao Yang, Yingzi Xue, Ming Zhang, Xuesong Yang & Yanhong Yu

  2. Department of Developmental and Regenerative Biology, College of Life Science and Technologies, Jinan University, Guangzhou, China

    Fang Liu, Anni Tan, Yingzi Xue, Ming Zhang, Luanjuan Xiao & Yanhong Yu

  3. Division of Histology and Embryology, Medical College, Jinan University, Guangzhou, China

    Renhao Yang & Xuesong Yang

  4. Department of Anesthesia, The First Affiliated Hospital, Jinan University, Guangzhou, China

    Lei Chen

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  1. Fang Liu
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  2. Anni Tan
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Correspondence to Yanhong Yu.

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Liu, F., Tan, A., Yang, R. et al. C1ql1/Ctrp14 and C1ql4/Ctrp11 promote angiogenesis of endothelial cells through activation of ERK1/2 signal pathway. Mol Cell Biochem 424, 57–67 (2017). https://doi.org/10.1007/s11010-016-2842-7

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  • DOI: https://doi.org/10.1007/s11010-016-2842-7

Keywords

  • C1ql1/Ctrp14
  • C1ql4/Ctrp11
  • Angiogenesis
  • ERK1/2
  • HUVECs
  • Chick yolk sac membrane