title: Matrix metalloproteinase-9 is up-regulated by CCL19/CCR7 interaction via PI3K/Akt pathway and is involved in CCL19-driven BMSCs migration.
abstract: C-C chemokine receptor 7 (CCR7) and its ligands CCL19 contributes to the directional migration of certain cancer cell lines, but its role in the migration of BMSCs remains vague. The aim of this study was to determine the possible interaction between CCL19-induced conditions and matrix metalloproteinases-9 (MMP9) expression in BMSCs. Cell migration using Transwell assay indicated that activation of CCR7 by its specific ligand, exogenous chemokine ligand 19 (CCL19), was associated with a significant linear increase. Western blot and real-time PCR indicated that CCL19/CCR7 significantly upregulated expression of MMP9, which is related to metastasis-associated genes. The CCL19/CCR7 interaction significantly enhanced phosphorylation of Akt, as measured by Western blot. P-Akt and MMP9 protein expression exhibited a time-dependent pattern, and the peak was at 48h. LY294002 significantly abolished the effects of exogenous CCL19. These results suggest that CCL19/CCR7 contributes to the migration of BMSCs by upregulating MMP9 potentially via the PI3K/Akt pathway.
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital of China Medical University, Shenyang 110001, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital of China Medical University, Shenyang 110001, China. Electronic address: tgj188@gmail.com.
authors.forename: Guanjun
authors.initials: G
authors.lastname: Tu
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital of China Medical University, Shenyang 110001, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Lv
authors.affiliation: Department of Vascular Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Long
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital of China Medical University, Shenyang 110001, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Cong
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital of China Medical University, Shenyang 110001, China.
authors.forename: Yaxin
authors.initials: Y
authors.lastname: Han
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D002478:Cells, Cultured; D054415:Chemokine CCL19 / Q000378:metabolism*; D002867:Chromones / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D054400:Receptors, CCR7 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D054415:Chemokine CCL19; D002867:Chromones; D020780:Matrix Metalloproteinase 9; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; D054400:Receptors, CCR7; C515372:Ccr7 protein, rat; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C572337:Mmp9 protein, rat
keywords: BMSCs; CCL19; CCR7; MMP9; Migration; P-Akt