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

ABSTRACT: 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.

SUBMITTER: Shen B

PROVIDER: S-EPMC3824990 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Store operated Ca2+ entry (SOCE) controls ameloblast cell function and enamel development

Project description:Abstarct:Mutations in the endoplasmic reticulum (ER) Ca2+ sensor stromal interaction molecule 1 (STIM1) result is a number of disease states including abnormal enamel formation. However, these defects in enamel have remained unclear given a lack of animal models available. We generated Stim1/2K14Cre mice to ablate the activity of STIM1 and its homologue STIM2 in enamel cells. These mice showed impaired Ca2+ entry in enamel cells and although enamel formed, it was severely hypomineralized and mechanically weak. RNA-sequencing of enamel cells provided a global overview of loss of Ca2+ sensor activity. ER stress markers associated with unfolded protein response (UPR) were increased. Cell morphology was altered showing loss of the typical ruffled-border and mislocalized mitochondria. We also identified decreased glutathione system and potentially associated with this, increased ROS and abnormal mitochondria. The Ca2+ extrusion system and enamel gene expression were also altered. These data might represent the first in vivo study linking Stim1/2 ablation with increased UPR function, decreased glutathione metabolism, increased ROS and abnormal mitochondria. Loss of ER Ca2+ sensors Stim1/2 in enamel cells has substantial detrimental effects at the cell and mineral phase level.

2017-01-17 | GSE93655 | GEO

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