Sublytic C5b-9 induces proliferation of human aortic smooth muscle cells: Role of mitogen activated protein kinase and phosphatidylinositol 3-kinase |
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| Institution: | 1. Department of Vascular Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China;2. Department of Vascular Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China;3. Department of Ultrasound, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China;4. Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China;1. CNC — Center for Neuroscience and Cell Biology, University of Coimbra, Largo Marquês de Pombal, 3004-517 Coimbra, Portugal;2. CFE — Center for Functional Ecology, Department of Life Sciences, University of Coimbra, Calçada Martins de Freitas 3000-456 Coimbra, Portugal;3. Departament d''Ecologia, Facultat de Biologia, Universitat de Barcelona, Av. Diagonal 645, 08028 Barcelona, Spain;4. Departament de Bioquímica i Biologia Molecular, Facultat de Farmàcia, Universitat de Barcelona, Av. Joan XXIII s/n, 08028 Barcelona, Spain |
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| Abstract: | Proliferation of vascular smooth muscle cells contributes to initimal hyperplasia during atherogenesis, but the factors regulating their proliferation are not well known. In the present study we report that sublytic C5b-9 assembly induced proliferation of differentiated human aortic smooth muscle cells (ASMC) in culture. Cell cycle re-entry occurred through activation of cdk4, cdk2 kinase and the reduction of p21 cell cycle inhibitor. We also investigated if C5b-9 cell cycle induction is mediated through activation of mitogen activated protein kinase (MAPK) pathways. Extracellular signal regulated kinase (ERK) 1 activity was significantly increased, while c-jun NH2-terminal kinase (JNK) 1 and p38 MAPK activity were only transiently increased. Pretreatment with wortmannin inhibits ERK1 activation by C5b-9, suggesting the involvement of phosphatidylinositol 3-kinase (PI 3-kinase). Both PI 3-kinase and p70 S6 kinase were activated by C5b-9 but not by C5b6. C5b-9 induced DNA synthesis was abolished by pretreatment with inhibitors of ERK1 and PI 3-kinase, but not by p38 MAPK. These data indicated that ERK1 and PI 3-kinase play a major role in C5b-9 induced ASMC proliferation. |
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