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STIM‐1 and ORAI‐1 channel mediate angiotensin‐II‐induced expression of Egr‐1 in vascular smooth muscle cells
Author(s) -
SimoCheyou Estelle R.,
Tan Ju Jing,
Grygorczyk Ryszard,
Srivastava Ashok K.
Publication year - 2017
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.25810
Subject(s) - vascular smooth muscle , angiotensin ii , microbiology and biotechnology , chemistry , smooth muscle , biology , endocrinology , biochemistry , receptor
An upregulation of Egr‐1 expression has been reported in models of atherosclerosis and intimal hyperplasia and, various vasoactive peptides and growth promoting stimuli have been shown to induce the expression of Egr‐1 in vascular smooth muscle cells (VSMC). Angiotensin‐II (Ang‐II) is a key vasoactive peptide that has been implicated in the pathogenesis of vascular diseases. Ang‐II elevates intracellular Ca 2+ through activation of the store‐operated calcium entry (SOCE) involving an inositol‐3‐phosphate receptor (IP3R)‐coupled depletion of endoplasmic reticular Ca 2+ and a subsequent activation of the stromal interaction molecule 1 (STIM‐1)/Orai‐1 complex. However, the involvement of IP3R/STIM‐1/Orai‐1‐Ca 2+ ‐dependent signaling in Egr‐1 expression in VSMC remains unexplored. Therefore, in the present studies, we have examined the role of Ca 2+ signaling in Ang‐II‐induced Egr‐1 expression in VSMC and investigated the contribution of STIM‐1 or Orai‐1 in mediating this response. 2‐aminoethoxydiphenyl borate (2‐APB), a dual non‐competitive antagonist of IP3R and inhibitor of SOCE, decreased Ang‐II‐induced Ca 2+ release and attenuated Ang‐II‐induced enhanced expression of Egr‐1 protein and mRNA levels. Egr‐1 upregulation was also suppressed following blockade of calmodulin and CaMKII. Furthermore, RNA interference‐mediated depletion of STIM‐1 or Orai‐1 attenuated Ang‐II‐induced Egr‐1 expression as well as Ang‐II‐induced phosphorylation of ERK1/2 and CREB. In addition, siRNA‐induced silencing of CREB resulted in a reduction in the expression of Egr‐1 stimulated by Ang‐II. In summary, our data demonstrate that Ang‐II‐induced Egr‐1 expression is mediated by STIM‐1/Orai‐1/Ca 2+ ‐dependent signaling pathways in A‐10 VSMC.