Phosphate-induced ORAI1 expression and store-operated Ca2+ entry in aortic smooth muscle cells

Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte
Ke MaFlorian Lang

Abstract

Compromised renal phosphate elimination in chronic kidney disease (CKD) leads to hyperphosphatemia, which in turn triggers osteo-/chondrogenic signaling in vascular smooth muscle cells (VSMCs) and vascular calcification. Osteo-/chondrogenic transdifferentiation of VSMCs leads to upregulation of the transcription factors MSX2, CBFA1, and SOX9 as well as tissue-nonspecific alkaline phosphatase (ALPL) which fosters calcification by degrading the calcification inhibitor pyrophosphate. Osteo-/chondrogenic signaling in VSMCs involves the serum- and glucocorticoid-inducible kinase SGK1. As shown in other cell types, SGK1 is a powerful stimulator of ORAI1, a Ca2+-channel accomplishing store-operated Ca2+-entry (SOCE). ORAI1 is stimulated following intracellular store depletion by the Ca2+ sensor STIM1. The present study explored whether phosphate regulates ORAI1 and/or STIM1 expression and, thus, SOCE in VSMCs. To this end, primary human aortic smooth muscle cells (HAoSMCs) were exposed to the phosphate donor β-glycerophosphate. Transcript levels were estimated by qRT-PCR, protein abundance by western blotting, ALPL activity by colorimetry, calcification by alizarin red S staining, cytosolic Ca2+-concentration ([Ca2+]i) by Fura-2-fluor...Continue Reading

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Citations

Oct 25, 2020·Proceedings of the National Academy of Sciences of the United States of America·Jessie HuangSteven S An
Jan 8, 2021·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Xuexue ZhuFlorian Lang
Feb 1, 2021·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Martina FegerMichael Föller
Mar 30, 2021·Clinical Kidney Journal·Paola Ciceri, Mario Cozzolino
Apr 4, 2021·International Journal of Molecular Sciences·Kuo ZhouFlorian Lang
May 4, 2021·Frontiers in Cell and Developmental Biology·Heba ShawerMarc A Bailey
Jun 6, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Yanyan ZhangXiangchun Shen

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Methods Mentioned

BETA
nuclear translocation
PCR
PCRs

Software Mentioned

Metafluor
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