title: CXCL16 induces angiogenesis in autocrine signaling pathway involving hypoxia-inducible factor 1α in human umbilical vein endothelial cells.
abstract: Chemokine (C-X-C motif) ligand 16 (CXCL16) is a new angiogenic factor inducing angiogenesis via extracellular signal-regulated kinases pathway. To further understand the molecular mechanism underlying CXCL16‑induced angiogenesis, we explored involvement of other relevant pathways in CXCL16-induced angiogenesis. In the present study, we investigated the mechanisms underlying CXCL16-induced angiogenesis in human umbilical vein endothelial cells (HUVECs). CXCL16 promoted HUVEC proliferation, tube formation and migration. Enzyme-linked immunosorbent assay revealed that CXCL16 induced vascular endothelial growth factor secretion from HUVECs. Western blot analysis showed that CXCL16 increased the level of hypoxia‑inducible factor 1α, p-extracellular signal-regulated kinases (ERK), p-p38 and p-Akt dose- and time-dependently. ERK-, p38- and Akt-selective inhibitors significantly suppressed HUVEC proliferation, migration, tube formation and hypoxia-inducible factor 1α (HIF-1α) expression induced by CXCL16. Furthermore, CXCL16 peptides induced CXCL16 secretion via ERK, p38 and Akt pathways, which was suppressed by HIF-1α-selective inhibitor PX12. Our data suggest that CXCL16 induces angiogenesis in autocrine manner via ERK, Akt, p38 pathways and HIF-1α modulation.
authors.affiliation: Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Biophysics, University of Saarland, D-66421 Homburg, Germany.
authors.forename: Renping
authors.initials: R
authors.lastname: Zhao
authors.affiliation: Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Sensen
authors.initials: S
authors.lastname: Lin
authors.affiliation: Department of Molecular Physiology, University of Saarland, D-66421 Homburg, Germany.
authors.forename: Xianshu
authors.initials: X
authors.lastname: Bai
authors.affiliation: Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Luyong
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Shengtao
authors.initials: S
authors.lastname: Yuan
authors.affiliation: Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Sun
mesh_terms: D019898:Autocrine Communication / Q000235:genetics*; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis* / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D051116:Receptors, Scavenger / Q000096:biosynthesis* / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics
chemical_list: C423727:CXCL16 protein, human; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051116:Receptors, Scavenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D051057:Proto-Oncogene Proteins c-akt