Store-Operated Ca2+ Entry Channels Regulate Cell Growth and Migration in Human Cardiac C-Kit+ Progenitor Cells

Abstract

Background and objective: It is believed that cardiac c-kit+ progenitor cells maintain cardiac homeostasis and have the potential of multipotent differentiation and myocardial repair. However, cellular physiology is not well understood in cardiac c-kit+ progenitor cells. The present study investigated the functional store-operated Ca2+ entry (SOCE) channels and the potential role in regulating cell proliferation and migration in human cardiac c-kit+ progenitor cells.Methods: Multiple techniques were employed in the present study, including confocal scanning microscope, RT-PCR, Western blot analysis, co-immunoprecipitation, and cell proliferation and migration assays.Results: We found that Ca2+ influx through SOCE channels was inhibited by La3+ or 2-aminoethoxydiphenyl borate. Genes and proteins of the SOCE components TRPC1, STIM1 and Orai1 were abundant in human cardiac c-kit+ progenitor cells, and the protein-protein interaction between TRPC1, STIM1 and Orai1 was revealed by co-immunoprecipitation. Silence of TRPC1, STIM1, or Orai1 with the corresponding siRNA significantly reduced the Ca2+ influx through SOCE channels. Interestingly, knockdown of TRPC1, STIM1, or Orai1 decreased cell proliferation by reducing cyclin D1 and cyclin E, while inhibited cell migration via reducing p-Akt kinase.Conclusion: Our results demonstrate the novel information that TRPC1, STIM1 and Orai1 are the major components of SOCE channels in human cardiac c-kit+ cells. They regulate cell proliferation by increasing cyclin D1 and cyclin E, modulate cell migration by activating p-Akt.