title: Bradykinin regulates cell growth and migration in cultured human cardiac c-Kit+ progenitor cells.
abstract: Bradykinin is a well-known endogenous vasoactive peptide. The present study investigated the bradykinin receptor expression in human cardiac c-Kit+ progenitor cells and the potential role of bradykinin in regulating cell cycling progression and mobility. It was found that mRNA and protein of bradykinin type 2 receptors, but not bradykinin type 1 receptors, were abundant in cultured human cardiac c-Kit+ progenitor cells. Bradykinin (1-10 nM) stimulated cell growth and migration in a concentration-dependent manner. The increase of cell proliferation was related to promoting G0/G1 transition into G2/M and S phase. Western blots revealed that bradykinin significantly increased pAkt and pERK1/2 as well as cyclin D1, which were countered by HOE140 (an antagonist of bradykinin type 2 receptors) or by silencing bradykinin type 2 receptors. The increase of pAkt, pERK1/2 and cyclin D1 by bradykinin was prevented by the PI3K inhibitor Ly294002, the PLC inhibitors U73122 and neomycin, and/or the PKC inhibitor chelerythrine and the MAPK inhibitor PD98059. Our results demonstrate the novel information that bradykinin promotes cell cycling progression and migration in human cardiac c-Kit+ progenitor cells via activating PI3K, PLC, PKC, cyclin D1, pERK1/2, and pAkt.
authors.affiliation: Xiamen Cardiovascular Hospital, Xiamen University, Xiamen, Fujian, China.|Department of Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.affiliation: Xiamen Cardiovascular Hospital, Xiamen University, Xiamen, Fujian, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Xiamen Cardiovascular Hospital, Xiamen University, Xiamen, Fujian, China.|Department of Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong, China.
authors.forename: Gui-Rong
authors.initials: GR
authors.lastname: Li
mesh_terms: D015153:Blotting, Western; D001920:Bradykinin / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects* / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects* / Q000235:genetics; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006325:Heart Atria / Q000166:cytology; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D034622:RNA Interference; D043783:Receptor, Bradykinin B1 / Q000235:genetics / Q000378:metabolism; D043782:Receptor, Bradykinin B2 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D019938:Cyclin D1; D019869:Phosphatidylinositol 3-Kinases; D019009:Proto-Oncogene Proteins c-kit; D051057:Proto-Oncogene Proteins c-akt; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D010738:Type C Phospholipases; D001920:Bradykinin
keywords: Bradykinin; Pathology Section; bradykinin receptor 2; human cardiac c-Kit+ progenitor cells; migration; proliferation