Involvement of STIM1 and Orai1 in EGF-mediated cell growth in retinal pigment epithelial cells

Journal of Biomedical Science

Wei-Chiao Chang³  Ben-Kuen Chen⁶  Wen-Li Hsu⁵  Ming-Feng Hou⁴  Hsuan-Hung Lee¹  Li-Teh Liu⁷  Siou-Jin Chiu¹  Yao-Ting Tsai¹  I-Hui Yang² 

[1] Department of Medical Genetics, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan;Department of Ophthalmology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan;Department of Pharmacy, Taipei Medical University-Wanfang Hospital, Taipei, Taiwan;Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan;Center for Resources, Research and Development, Kaohsiung Medical University, Kaohsiung, Taiwan;Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan;Department of Medical Laboratory Science and Biotechnology, College of Medicine and Life Science, Chung-Hwa University of Medical Technology, Tainan, Taiwan

关键词: Proliferative vitreoretinopathy;    Retinal pigment epithelial cell;    Store-operated calcium channel;    Orai1;    STIM1;   

Others  :  823794
DOI  :  10.1186/1423-0127-20-41

 received in 2013-01-15, accepted in 2013-06-18,  发布年份 2013

【 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.

【 授权许可】

   
2013 Yang et al.; licensee BioMed Central Ltd.

【 图 表 】

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