A stromal interaction molecule 1 variant up-regulates matrix metalloproteinase-2 expression by strengthening nucleoplasmic Ca2+ signaling

Fengrong Chen, Liping Zhu, Lei Cai, Jiwei Zhang, Xianqin Zeng, Jiansha Li, Yuan Su, Qinghua Hu
2016 BBA - Molecular Cell Research  
Very recent studies hold promise to reveal the role of stromal interaction molecule 1 (STIM1) in non-storeoperated Ca 2+ entry. Here we showed that in contrast to cytoplasmic membrane redistribution as previously noted, human umbilical vein endothelial STIM1 with a T-to-C nucleotide transition resulting in an amino acid substitution of leucine by proline in the signal peptide sequence translocated to perinuclear membrane upon intracellular Ca 2+ depletion, amplified nucleoplasmic Ca 2+
more » ... smic Ca 2+ signaling through ryanodine receptor-dependent pathway, and enhanced the subsequent cAMP responsive element binding protein activity, matrix metalloproteinase-2 (MMP-2) gene expression, and endothelial tube forming. The abundance of mutated STIM1 and the MMP-2 expression were higher in native human umbilical vein endothelial cells of patients with gestational hypertension than controls and were significantly correlated with blood pressure. These findings broaden our understanding about structure-function bias of STIM1 and offer unique insights into its application in nucleoplasmic Ca 2+ , MMP-2 expression, endothelial dysfunction, and pathophysiological mechanism(s) of gestational hypertension.
doi:10.1016/j.bbamcr.2016.01.007 pmid:26775216 fatcat:r5kucaraqnekrhqhb3alhfn5i4