Molecular and Cellular Biochemistry

, Volume 424, Issue 1–2, pp 57–67 | Cite as

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

  • Fang Liu
  • Anni Tan
  • Renhao Yang
  • Yingzi Xue
  • Ming Zhang
  • Lei Chen
  • Luanjuan Xiao
  • Xuesong Yang
  • Yanhong Yu


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.


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



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.

Supplementary material

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Supplementary material 1 (DOCX 17 kb)
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Supplementary material 2 (TIFF 4481 kb)
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Supplementary material 3 (TIFF 4289 kb)


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Key Laboratory for Regenerative Medicine (JNU-CUHK) Ministry of EducationJinan UniversityGuangzhouChina
  2. 2.Department of Developmental and Regenerative Biology, College of Life Science and TechnologiesJinan UniversityGuangzhouChina
  3. 3.Division of Histology and Embryology, Medical CollegeJinan UniversityGuangzhouChina
  4. 4.Department of Anesthesia, The First Affiliated HospitalJinan UniversityGuangzhouChina

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