Roles of store-operated Ca2+ channels in regulating cell cycling and migration of human cardiac c-kit+ progenitor cells
Roles of store-operated Ca2+ channels in regulating cell cycling and migration of human cardiac c-kit+ progenitor cells
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DOI：
10.1152/ajpheart.00260.2015
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发表时间：
2015-11-15
影响因子：
4.8
通讯作者：
Li, Gui-Rong
中科院分区：
文献类型：
--
作者：
Che, Hui;Li, Gang;Li, Gui-Rong
心脏c-kit（+）祖细胞对维持心脏稳态很重要，并可能有助于心肌修复。然而，人类心脏c-kit（+）祖细胞的细胞生理学还没有得到很好的理解。本研究采用共聚焦显微镜、RT-PCR、Western blot、免疫共沉淀、细胞增殖和迁移试验，研究了功能性钙库操纵的钙离子进入（SOCE）通道及其在调节细胞周期和迁移中的潜在作用。我们发现SOCE通道介导了人心脏c-kit（+）祖细胞的Ca ~（2+）内流，TRPC 1、STIM 1和Orai 1参与了SOCE通道的形成。用相应的siRNA沉默TRPC 1、STIM 1或Orai 1显著降低了通过SOCE通道的Ca 2+信号传导，降低了细胞增殖和迁移，并降低了细胞周期蛋白D1、细胞周期蛋白E和/或p-Akt的表达。我们的研究结果表明，新的信息，钙离子信号通过SOCE通道调节细胞周期和迁移通过激活细胞周期蛋白D1，细胞周期蛋白E，和/或p-Akt在人心脏c-kit（+）细胞。
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 Ca2+ 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 Ca2+ 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 Ca2+ 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 Ca2+ 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.