Attenuated mesangial cell proliferation related to store-operated Ca2+ entry in aged rat: the role of STIM 1 and Orai 1
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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.
KeywordsAging STIM 1 Orai 1 Glomerular mesangial cell Proliferation
This work was supported by grants from NSF of China (grant no. 30800384); NSF of Anhui Province Department of Education (grant no. KJ2008B292); Scientific Research of BSKY (grant nos. XJ201106 and XJ200913) and Young Prominent Investigator Supporting Program from Anhui Medical University; Anhui Provincial Natural Science Foundation (11040606M171 and 1108085J11); and National Institutes of Health (NIH) of USA (5RO1DK079968-01A2m Ma).
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