- 作者: I-Hui Yang, Yao-Ting Tsai, Siou-Jin Chiu, Li-Teh Liu, Hsuan-Hung Lee, Ming-Feng Hou, Wen-Li Hsu, Ben-Kuen Chen and Wei-Chiao Chang
- 作者服務機構: Department of Medical Genetics, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, R.O.C
- 中文摘要: --
- 英文摘要:
Background: In non-excitable cells, one major route for calcium entry is through store-operated calcium (SOC) channels in the plasma membrane. These channels are activated by the emptying of intracellular Ca2+ store. STIM1 and Orai1 are major regulators of SOC channels. In this study, we explored the functions of STIM1 and Orai1 in epidermal growth factor (EGF)-induced cell proliferation and migration in retinal pigment epithelial cells (ARPE-19 cell line).
Results: EGF triggers cell proliferation and migration in ARPE-19 cells. Cell proliferation and migration involve STIM1 and Orai1, as well as phosphorylation of extracellular signal-regulated protein kinase (ERK) 1/2, and Akt. Pharmacological inhibitors of SOC channels and siRNA of Orai1 and STIM1 suppress cell proliferation and migration. Pre-treatment of mitogen-activated protein kinase kinase (MEK) inhibitors and a phosphatidylinositol 3 kinases (PI3K) inhibitor attenuated cell proliferation and migration. However, inhibition of the SOC channels failed to prevent EGF-mediated ERK 1/2 and Akt phosphorylation.
Conclusions: Our results showed that STIM1, Orai1, ERK 1/2, and Akt are key determinants of EGF-mediated cell growth in ARPE-19 cells. EGF is a potent growth molecule that has been linked to the development of PVR, and therefore, STIM1, Orai1, as well as the MEK/ERK 1/2 and PI3K/Akt pathways, might be potential therapeutic targets for drugs aimed at treating such disorders. - 中文關鍵字: --
- 英文關鍵字: STIM1, Orai1, Store-operated calcium channel, Retinal pigment epithelial cell, Proliferative vitreoretinopathy