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
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.

Keywords

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

Notes

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.

Supplementary material

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Supplementary material 1 (DOCX 17 kb)
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Supplementary material 2 (TIFF 4481 kb)
11010_2016_2842_MOESM3_ESM.tif (4.2 mb)
Supplementary material 3 (TIFF 4289 kb)

References

  1. 1.
    Kishore U, Gaboriaud C, Waters P, Shrive AK, Greenhough TJ, Reid KB, Sim RB, Arlaud GJ (2004) C1q and tumor necrosis factor superfamily: modularity and versatility. Trends Immunol 25:551–561. doi: 10.1016/j.it.2004.08.006 CrossRefPubMedGoogle Scholar
  2. 2.
    Seldin MM, Tan SY, Wong GW (2014) Metabolic function of the CTRP family of hormones. Rev Endocr & Metab Disord 15:111–123. doi: 10.1007/s11154-013-9255-7 CrossRefGoogle Scholar
  3. 3.
    Iijima T, Miura E, Watanabe M, Yuzaki M (2010) Distinct expression of C1q-like family mRNAs in mouse brain and biochemical characterization of their encoded proteins. Eur J Neurosci 31:1606–1615. doi: 10.1111/j.1460-9568.2010.07202.x PubMedGoogle Scholar
  4. 4.
    Wei ZK, Seldin MM, Natarajan N, Djemal DC, Peterson JM, Wong GW (2013) C1q/Tumor tecrosis factor-related protein 11 (CTRP11), a novel adipose stroma-derived regulator of adipogenesis. J Biol Chem 288:10214–10229. doi: 10.1074/jbc.M113.458711 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Bolliger MF, Martinelli DC, Sudhof TC (2011) The cell-adhesion G protein-coupled receptor BAI3 is a high-affinity receptor for C1q-like proteins. Proc Natl Acad Sci USA 108:2534–2539CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Schaffler A, Buechler C (2012) CTRP family: linking immunity to metabolism. Trends Endocrinol Metab 23:194–204. doi: 10.1016/j.tem.2011.12.003 CrossRefPubMedGoogle Scholar
  7. 7.
    Wei Z, Peterson JM, Wong GW (2011) Metabolic regulation by C1q/TNF-related protein-13 (CTRP13): activation OF AMP-activated protein kinase and suppression of fatty acid-induced JNK signaling. J Biol Chem 286:15652–15665. doi: 10.1074/jbc.M110.201087 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Sigoillot SM, Iyer K, Binda F, Gonzalez-Calvo I, Talleur M, Vodjdani G, Isope P, Selimi F (2015) The secreted protein C1QL1 and its receptor BAI3 control the synaptic connectivity of excitatory inputs converging on cerebellar purkinje cells. Cell Rep. doi: 10.1016/j.celrep.2015.01.034 PubMedGoogle Scholar
  9. 9.
    Kakegawa W, Mitakidis N, Miura E, Abe M, Matsuda K, Takeo YH, Kohda K, Motohashi J, Takahashi A, Nagao S, Muramatsu S, Watanabe M, Sakimura K, Aricescu AR, Yuzaki M (2015) Anterograde C1ql1 signaling is required in order to determine and maintain a single-winner climbing fiber in the mouse cerebellum. Neuron 85:316–329. doi: 10.1016/j.neuron.2014.12.020 CrossRefPubMedGoogle Scholar
  10. 10.
    Matsuda K, Budisantoso T, Mitakidis N, Sugaya Y, Miura E, Kakegawa W, Yamasaki M, Konno K, Uchigashima M, Abe M, Watanabe I, Kano M, Watanabe M, Sakimura K, Aricescu AR, Yuzaki M (2016) Transsynaptic modulation of kainate receptor functions by C1q-like proteins. Neuron 90:752–767. doi: 10.1016/j.neuron.2016.04.001 CrossRefPubMedGoogle Scholar
  11. 11.
    Martinelli DC, Chew KS, Rohlmann A, Lum MY, Ressl S, Hattar S, Brunger AT, Missler M, Sudhof TC (2016) Expression of C1ql3 in discrete neuronal populations controls efferent synapse numbers and diverse behaviors. Neuron. doi: 10.1016/j.neuron.2016.07.002 PubMedGoogle Scholar
  12. 12.
    Bossi F, Tripodo C, Rizzi L, Bulla R, Agostinis C, Guarnotta C, Munaut C, Baldassarre G, Papa G, Zorzet S, Ghebrehiwet B, Ling GS, Botto M, Tedesco F (2014) C1q as a unique player in angiogenesis with therapeutic implication in wound healing. Proc Natl Acad Sci USA 111:4209–4214. doi: 10.1073/pnas.1311968111 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Ouchi N, Kobayashi H, Kihara S, Kumada M, Sato K, Inoue T, Funahashi T, Walsh K (2004) Adiponectin stimulates angiogenesis by promoting cross-talk between AMP-activated protein kinase and Akt signaling in endothelial cells. J Biol Chem 279:1304–1309. doi: 10.1074/jbc.M310389200 CrossRefPubMedGoogle Scholar
  14. 14.
    Kee HJ, Ahn KY, Choi KC, Won Song J, Heo T, Jung S, Kim JK, Bae CS, Kim KK (2004) Expression of brain-specific angiogenesis inhibitor 3 (BAI3) in normal brain and implications for BAI3 in ischemia-induced brain angiogenesis and malignant glioma. FEBS Lett 569:307–316CrossRefPubMedGoogle Scholar
  15. 15.
    Yu Y, Huang H, Wang Y, Yu Y, Yuan S, Huang S, Pan M, Feng K, Xu A (2008) A novel C1q family member of amphioxus was revealed to have a partial function of vertebrate C1q molecule. J Immunol 181:7024–7032CrossRefPubMedGoogle Scholar
  16. 16.
    Jaffe EA, Nachman RL, Becker CG, Minick CR (1973) Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J Clin Invest 52:2745–2756. doi: 10.1172/JCI107470 CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Wang G, Zhang N, Wei YF, Jin YM, Zhang SY, Cheng X, Ma ZL, Zhao SZ, Chen YP, Chuai M, Hocher B, Yang X (2015) The impact of high-salt exposure on cardiovascular development in the early chick embryo. J Exp Biol 218:3468–3477. doi: 10.1242/jeb.129486 CrossRefPubMedGoogle Scholar
  18. 18.
    Patan S (2004) Vasculogenesis and angiogenesis. Cancer Treat Res 117:3–32CrossRefPubMedGoogle Scholar
  19. 19.
    Folkman J (2003) Fundamental concepts of the angiogenic process. Curr Mol Med 3:643–651. doi: 10.2174/1566524033479465 CrossRefPubMedGoogle Scholar
  20. 20.
    Mei J, Zhang QY, Li Z, Lin S, Gui JF (2008) C1q-like inhibits p53-mediated apoptosis and controls normal hematopoiesis during zebrafish embryogenesis. Dev Biol 319:273–284. doi: 10.1016/j.ydbio.2008.04.022 CrossRefPubMedGoogle Scholar
  21. 21.
    Carmeliet P (2005) Angiogenesis in life, disease and medicine. Nature 438:932–936. doi: 10.1038/nature04478 CrossRefPubMedGoogle Scholar
  22. 22.
    Mason JC, Lidington EA, Ahmad SR, Haskard DO (2002) bFGF and VEGF synergistically enhance endothelial cytoprotection via decay-accelerating factor induction. Am J Physiol Cell Physiol 282:C578–C587. doi: 10.1152/ajpcell.00339.2001 CrossRefPubMedGoogle Scholar
  23. 23.
    Aiken J, Birot O (2016) The vascular endothelial growth factor-A phosphorylates murine double minute-2 on its serine 166 via the extracellular signal-regulated kinase 1/2 and p90 ribosomal S6 kinase in primary human endothelial cells. Biochem Biophys Res Commun. doi: 10.1016/j.bbrc.2016.08.150 PubMedGoogle Scholar
  24. 24.
    Clement DL, Mally S, Stock C, Lethan M, Satir P, Schwab A, Pedersen SF, Christensen ST (2013) PDGFRalpha signaling in the primary cilium regulates NHE1-dependent fibroblast migration via coordinated differential activity of MEK1/2-ERK1/2-p90RSK and AKT signaling pathways. J Cell Sci 126:953–965. doi: 10.1242/jcs.116426 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Gaboriaud C, Juanhuix J, Gruez A, Lacroix M, Darnault C, Pignol D, Verger D, Fontecilla-Camps JC, Arlaud GJ (2003) The crystal structure of the globular head of complement protein C1q provides a basis for its versatile recognition properties. J Biol Chem 278:46974–46982. doi: 10.1074/jbc.M307764200 CrossRefPubMedGoogle Scholar
  26. 26.
    Ghebrehiwet B, Hosszu KK, Valentino A, Peerschke EI (2012) The C1q family of proteins: insights into the emerging non-traditional functions. Front Immunol 3:52. doi: 10.3389/fimmu.2012.00052 CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Adya R, Tan BK, Chen J, Randeva HS (2012) Protective actions of globular and full-length adiponectin on human endothelial cells: novel insights into adiponectin-induced angiogenesis. J Vasc Res 49:534–543. doi: 10.1159/000338279 CrossRefPubMedGoogle Scholar
  28. 28.
    Bobbert P, Antoniak S, Schultheiss HP, Rauch U (2008) Globular adiponectin but not full-length adiponectin induces increased procoagulability in human endothelial cells. J Mol Cell Cardiol 44:388–394. doi: 10.1016/j.yjmcc.2007.10.018 CrossRefPubMedGoogle Scholar
  29. 29.
    Stephenson JR, Purcell RH, Hall RA (2014) The BAI subfamily of adhesion GPCRs: synaptic regulation and beyond. Trends Pharmacol Sci 35:208–215. doi: 10.1016/j.tips.2014.02.002 CrossRefPubMedPubMedCentralGoogle Scholar

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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