title: C1ql1/Ctrp14 and C1ql4/Ctrp11 promote angiogenesis of endothelial cells through activation of ERK1/2 signal pathway.
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.
authors.affiliation: Key Laboratory for Regenerative Medicine (JNU-CUHK) Ministry of Education, Jinan University, Guangzhou, China.|Department of Developmental and Regenerative Biology, College of Life Science and Technologies, Jinan University, Guangzhou, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Key Laboratory for Regenerative Medicine (JNU-CUHK) Ministry of Education, Jinan University, Guangzhou, China.|Department of Developmental and Regenerative Biology, College of Life Science and Technologies, Jinan University, Guangzhou, China.
authors.forename: Anni
authors.initials: A
authors.lastname: Tan
authors.affiliation: Key Laboratory for Regenerative Medicine (JNU-CUHK) Ministry of Education, Jinan University, Guangzhou, China.|Division of Histology and Embryology, Medical College, Jinan University, Guangzhou, China.
authors.forename: Renhao
authors.initials: R
authors.lastname: Yang
authors.affiliation: Key Laboratory for Regenerative Medicine (JNU-CUHK) Ministry of Education, Jinan University, Guangzhou, China.|Department of Developmental and Regenerative Biology, College of Life Science and Technologies, Jinan University, Guangzhou, China.
authors.forename: Yingzi
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Key Laboratory for Regenerative Medicine (JNU-CUHK) Ministry of Education, Jinan University, Guangzhou, China.|Department of Developmental and Regenerative Biology, College of Life Science and Technologies, Jinan University, Guangzhou, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Anesthesia, The First Affiliated Hospital, Jinan University, Guangzhou, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Developmental and Regenerative Biology, College of Life Science and Technologies, Jinan University, Guangzhou, China.
authors.forename: Luanjuan
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Key Laboratory for Regenerative Medicine (JNU-CUHK) Ministry of Education, Jinan University, Guangzhou, China.|Division of Histology and Embryology, Medical College, Jinan University, Guangzhou, China.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Yang
authors.affiliation: Key Laboratory for Regenerative Medicine (JNU-CUHK) Ministry of Education, Jinan University, Guangzhou, China. yuyhong79@gmail.com.|Department of Developmental and Regenerative Biology, College of Life Science and Technologies, Jinan University, Guangzhou, China. yuyhong79@gmail.com.
authors.forename: Yanhong
authors.identifier: http://orcid.org/0000-0002-1652-201X
authors.initials: Y
authors.lastname: Yu
mesh_terms: D015922:Complement C1q / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D000072417:Protein Domains
chemical_list: C111500:ADGRB3 protein, human; D009419:Nerve Tissue Proteins; D015922:Complement C1q; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: Angiogenesis; C1ql1/Ctrp14; C1ql4/Ctrp11; Chick yolk sac membrane; ERK1/2; HUVECs