title: Roles of store-operated Ca2+ channels in regulating cell cycling and migration of human cardiac c-kit+ progenitor cells.
abstract: Cardiac c-kit(+) progenitor cells are important for maintaining cardiac homeostasis and can potentially contribute to myocardial repair. However, cellular physiology of human cardiac c-kit(+) progenitor cells is not well understood. The present study investigates the functional store-operated Ca(2+) entry (SOCE) channels and the potential role in regulating cell cycling and migration using confocal microscopy, RT-PCR, Western blot, coimmunoprecipitation, cell proliferation, and migration assays. We found that SOCE channels mediated Ca(2+) influx, and TRPC1, STIM1, and Orai1 were involved in the formation of SOCE channels in human cardiac c-kit(+) progenitor cells. Silencing TRPC1, STIM1, or Orai1 with the corresponding siRNA significantly reduced the Ca(2+) signaling through SOCE channels, decreased cell proliferation and migration, and reduced expression of cyclin D1, cyclin E, and/or p-Akt. Our results demonstrate the novel information that Ca(2+) signaling through SOCE channels regulates cell cycling and migration via activating cyclin D1, cyclin E, and/or p-Akt in human cardiac c-kit(+) cells.
authors.affiliation: Department of Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong, China; and.
authors.forename: Hui
authors.initials: H
authors.lastname: Che
authors.affiliation: Department of Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong, China; and Xiamen Cardiovascular Hospital, Medical College of Xiamen University, Xiamen, Fujian, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong, China; and.
authors.forename: Hai-Ying
authors.initials: HY
authors.lastname: Sun
authors.affiliation: Xiamen Cardiovascular Hospital, Medical College of Xiamen University, Xiamen, Fujian, China.
authors.forename: Guo-Sheng
authors.initials: GS
authors.lastname: Xiao
authors.affiliation: Xiamen Cardiovascular Hospital, Medical College of Xiamen University, Xiamen, Fujian, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong, China; and Xiamen Cardiovascular Hospital, Medical College of Xiamen University, Xiamen, Fujian, China grli8@outlook.com.
authors.forename: Gui-Rong
authors.identifier: http://orcid.org/0000-0002-9437-2280
authors.initials: GR
authors.lastname: Li
mesh_terms: D015220:Calcium Channels / Q000235:genetics*; D020013:Calcium Signaling / Q000235:genetics*; D002453:Cell Cycle / Q000235:genetics*; D054443:Cell Migration Assays; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000378:metabolism; D019927:Cyclin E / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D047468:Immunoprecipitation; D008565:Membrane Proteins / Q000235:genetics; D018613:Microscopy, Confocal; D009206:Myocardium / Q000166:cytology*; D009363:Neoplasm Proteins / Q000235:genetics; D000071740:ORAI1 Protein; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000378:metabolism*; D000071737:Stromal Interaction Molecule 1; D050052:TRPC Cation Channels / Q000235:genetics
chemical_list: C530104:CCND1 protein, human; D015220:Calcium Channels; D019927:Cyclin E; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; D034741:RNA, Small Interfering; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; D050052:TRPC Cation Channels; C096351:transient receptor potential cation channel, subfamily C, member 1; D019938:Cyclin D1; D019009:Proto-Oncogene Proteins c-kit; D051057:Proto-Oncogene Proteins c-akt
keywords: Ca2+ signaling; canonical transient receptor potential channels; cell cycling; human cardiac c-kit+ progenitor cells; migration; store-operated calcium entry channels