Shen Bing, Zhu Jinhang, Zhang Jin, Jiang Feifei, Wang Zhaoyi, Zhang Yang, Li Jie, Huang Dake, Ke Daoping, Ma Rong, Du Juan
Department of Physiology, Anhui Medical University, Hefei, China,
Age (Dordr). 2013 Dec;35(6):2193-202. doi: 10.1007/s11357-013-9511-5. Epub 2013 Jan 20.
Store-operated Ca(2+) entry (SOCE) is a common and ubiquitous mechanism regulating Ca(2+) influx into cells and participates in numerous biological processes including cell proliferation. Glomerular mesangial cells (GMCs) play a role in the regulation of the glomerular filtration rate. From a clinical point of view, many physiological functions alter with age. In the present study, we used angiotensin II, glucagon, and the sarco/endoplasmic reticulum membrane Ca(2+) pump inhibitor thapsigargin to deplete the internal Ca(2+) stores for the activation of SOCE. We found that SOCE was significantly attenuated in GMCs from aged (22-month-old) rats. The expression of SOCE-related components, stromal interaction molecule 1 (STIM 1) and Orai 1, in freshly isolated glomeruli notably decreased, and STIM 1 and Orai 1 puncta formation significantly reduced in primary-cultured GMCs in aged rats. Moreover, specific knockdown of STIM 1 and Orai 1 by small interfering RNA markedly suppressed SOCE and cell proliferation of GMCs isolated from young (3-month-old) rats. We conclude that the attenuation of GMCs proliferation can be attributed to the decreased SOCE partially caused by reduced expression of STIM 1 and Orai 1.
store-operated Ca(2+) entry (SOCE)是一种常见且普遍存在的调节Ca(2+)流入细胞的机制，并参与包括细胞增殖在内的众多生物学过程。肾小球系膜细胞（GMCs）在肾小球滤过率的调节中发挥作用。从临床角度来看，许多生理功能会随着年龄的增长而发生变化。在本研究中，我们使用血管紧张素II、胰高血糖素以及肌浆网/内质网膜Ca(2+)泵抑制剂毒胡萝卜素耗尽细胞内Ca(2+)储存以激活SOCE。我们发现，来自老年（22月龄）大鼠的GMCs中SOCE显著减弱。在新鲜分离的肾小球中，SOCE相关成分基质相互作用分子1（STIM 1）和Orai 1的表达明显降低，并且在老年大鼠原代培养的GMCs中，STIM 1和Orai 1点状结构的形成显著减少。此外，通过小干扰RNA特异性敲低STIM 1和Orai 1可显著抑制从年轻（3月龄）大鼠分离的GMCs的SOCE和细胞增殖。我们得出结论，GMCs增殖的减弱可部分归因于STIM 1和Orai 1表达降低导致的SOCE减少。
