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

作者：Chen, Fengrong; Zhu, Liping; Cai, Lei; Zhang, Jiwei; Zeng, Xianqin; Li, Jiansha; Su, Yuan; Hu, Qinghua^*

来源：Biochimica et Biophysica Acta-Molecular Cell Research, 2016, 1863(4): 617-629.

DOI：10.1016/j.bbamcr.2016.01.007

• STIM1
• Matrix metalloproteinase-2
• Nucleoplasmic Ca2+
• CAMP responsive element binding protein
• Gene expression

Very recent studies hold promise to reveal the role of stromal interaction molecule 1 (STIM1) in non-store operated Ca2+ 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 Ca2+ depletion, amplified nucleoplasmic Ca2+ 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 Ca2+, MMP-2 expression, endothelial dysfunction, and pathophysiological mechanism(s) of gestational hypertension.

• 出版日期2016-4
• 单位华中科技大学