Bradykinin-mediated Ca 2+ signalling regulates cell growth and mobility in human cardiac c-Kit + progenitor cells

• Published in: Journal of cellular and molecular medicine 2018-10, Vol.22 (10), p.4688-4699
• Main Authors: Li, Gang, Che, Hui, Wu, Wei-Yin, Jie, Ling-Jun, Xiao, Guo-Sheng, Wang, Yan, Li, Gui-Rong
• Format: Article
• Language: English
• Subjects: Bradykinin; Bradykinin - pharmacology; Calcium - metabolism; Calcium channels; Calcium influx; Calcium ions; Calcium Signaling - drug effects; Calcium signalling; Cardiomyopathy; Cations, Divalent; Cell cycle; Cell growth; Cell migration; Cell Movement - drug effects; Cell Proliferation - drug effects; Confocal microscopy; Cyclin D1; Cyclin D1 - genetics; Cyclin D1 - metabolism; Female; Flow cytometry; Gene Expression Regulation; Heart; Humans; Inositol 1,4,5-Trisphosphate Receptors - genetics; Inositol 1,4,5-Trisphosphate Receptors - metabolism; Ion Transport - drug effects; Male; Microscopy; Middle Aged; Mitogen-Activated Protein Kinase 1 - genetics; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - genetics; Mitogen-Activated Protein Kinase 3 - metabolism; Myocardium - cytology; Myocardium - metabolism; Neoplasm Proteins - antagonists & inhibitors; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Orai1 protein; ORAI1 Protein - antagonists & inhibitors; ORAI1 Protein - genetics; ORAI1 Protein - metabolism; Polymerase chain reaction; Primary Cell Culture; Progenitor cells; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Proto-Oncogene Proteins c-kit - antagonists & inhibitors; Proto-Oncogene Proteins c-kit - genetics; Proto-Oncogene Proteins c-kit - metabolism; Quinolizines - pharmacology; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; siRNA; Stem cells; Stem Cells - cytology; Stem Cells - drug effects; Stem Cells - metabolism; STIM1 protein; Stromal Interaction Molecule 1 - antagonists & inhibitors; Stromal Interaction Molecule 1 - genetics; Stromal Interaction Molecule 1 - metabolism; TRPC Cation Channels - antagonists & inhibitors; TRPC Cation Channels - genetics; TRPC Cation Channels - metabolism
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.13706

Our recent study showed that bradykinin increases cell cycling progression and migration of human cardiac c-Kit progenitor cells by activating pAkt and pERK1/2 signals. This study investigated whether bradykinin-mediated Ca signalling participates in regulating cellular functions in cultured human cardiac c-Kit progenitor cells using laser scanning confocal microscopy and biochemical approaches. It was found that bradykinin increased cytosolic free Ca ( ) by triggering a transient Ca release from ER IP3Rs followed by sustained Ca influx through store-operated Ca entry (SOCE) channel. Blockade of B2 receptor with HOE140 or IP3Rs with araguspongin B or silencing IP3R3 with siRNA abolished both Ca release and Ca influx. It is interesting to note that the bradykinin-induced cell cycle progression and migration were not observed in cells with siRNA-silenced IP3R3 or the SOCE component TRPC1, Orai1 or STIM1. Also the bradykinin-induced increase in pAkt and pERK1/2 as well as cyclin D1 was reduced in these cells. These results demonstrate for the first time that bradykinin-mediated increase in free via ER-IP3R3 Ca release followed by Ca influx through SOCE channel plays a crucial role in regulating cell growth and migration via activating pAkt, pERK1/2 and cyclin D1 in human cardiac c-Kit progenitor cells.