Attenuated mesangial cell proliferation related to store-operated Ca2+ entry in aged rat: the role of STIM 1 and Orai 1

被引:19
作者
Shen, Bing [1 ]
Zhu, Jinhang [1 ]
Zhang, Jin [1 ]
Jiang, Feifei [1 ]
Wang, Zhaoyi [1 ]
Zhang, Yang [3 ]
Li, Jie [1 ]
Huang, Dake [2 ]
Ke, Daoping [1 ]
Ma, Rong [4 ]
Du, Juan [1 ]
机构
[1] Anhui Med Univ, Dept Physiol, Hefei, Peoples R China
[2] Anhui Med Univ, Comprehens Lab, Basic Med Sch, Hefei, Peoples R China
[3] Anhui Prov Hosp, Hefei 230032, Peoples R China
[4] Univ N Texas, Hlth Sci Ctr Ft Worth, Dept Integrat Physiol, Ft Worth, TX USA
基金
美国国家卫生研究院;
关键词
Aging; STIM; 1; Orai; Glomerular mesangial cell; Proliferation; STROMAL INTERACTION MOLECULE-1; PROTEIN-KINASE-C; CALCIUM INFLUX; ENDOPLASMIC-RETICULUM; CHANNELS; CRAC; HOMEOSTASIS; SENSOR; TRPC4;
D O I
10.1007/s11357-013-9511-5
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
Store-operated Ca2+ entry (SOCE) is a common and ubiquitous mechanism regulating Ca2+ 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 Ca2+ pump inhibitor thapsigargin to deplete the internal Ca2+ 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.
引用
收藏
页码:2193 / 2202
页数:10
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