title: A stromal interaction molecule 1 variant up-regulates matrix metalloproteinase-2 expression by strengthening nucleoplasmic Ca2+ signaling.
abstract: 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.
authors.affiliation: Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong Science and Technology University (HUST), Wuhan 430030, People's Republic of China; Key Laboratory of Pulmonary Diseases of Ministry of Health of China, Tongji Medical College, Huazhong Science and Technology University (HUST), Wuhan 430030, People's Republic of China.
authors.forename: Fengrong
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong Science and Technology University (HUST), Wuhan 430030, People's Republic of China; Key Laboratory of Pulmonary Diseases of Ministry of Health of China, Tongji Medical College, Huazhong Science and Technology University (HUST), Wuhan 430030, People's Republic of China.
authors.forename: Liping
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong Science and Technology University (HUST), Wuhan 430030, People's Republic of China; Key Laboratory of Pulmonary Diseases of Ministry of Health of China, Tongji Medical College, Huazhong Science and Technology University (HUST), Wuhan 430030, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Cai
authors.affiliation: Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong Science and Technology University (HUST), Wuhan 430030, People's Republic of China; Key Laboratory of Pulmonary Diseases of Ministry of Health of China, Tongji Medical College, Huazhong Science and Technology University (HUST), Wuhan 430030, People's Republic of China.
authors.forename: Jiwei
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong Science and Technology University (HUST), Wuhan 430030, People's Republic of China; Key Laboratory of Pulmonary Diseases of Ministry of Health of China, Tongji Medical College, Huazhong Science and Technology University (HUST), Wuhan 430030, People's Republic of China.
authors.forename: Xianqin
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Key Laboratory of Pulmonary Diseases of Ministry of Health of China, Tongji Medical College, Huazhong Science and Technology University (HUST), Wuhan 430030, People's Republic of China; Department of Pathology, Tongji Hospital, Tongji Medical College, Huazhong Science and Technology University (HUST), Wuhan 430030, People's Republic of China.
authors.forename: Jiansha
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Pulmonary Diseases of Ministry of Health of China, Tongji Medical College, Huazhong Science and Technology University (HUST), Wuhan 430030, People's Republic of China; Department of Respiratory Medicine, Union Hospital, Tongji Medical College, Huazhong Science and Technology University (HUST), Wuhan 430030, People's Republic of China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Su
authors.affiliation: Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong Science and Technology University (HUST), Wuhan 430030, People's Republic of China; Key Laboratory of Pulmonary Diseases of Ministry of Health of China, Tongji Medical College, Huazhong Science and Technology University (HUST), Wuhan 430030, People's Republic of China; Key Laboratory of Molecular Biophysics of the Ministry of Education, Huazhong Science and Technology University (HUST), Wuhan 430030, People's Republic of China. Electronic address: qinghuaa@mails.tjmu.edu.cn.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Hu
mesh_terms: D020013:Calcium Signaling / Q000235:genetics; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D046110:Hypertension, Pregnancy-Induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007231:Infant, Newborn; D020778:Matrix Metalloproteinase 2 / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D050505:Mutant Proteins / Q000502:physiology; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D011247:Pregnancy; D000071737:Stromal Interaction Molecule 1; D015854:Up-Regulation / Q000235:genetics
chemical_list: D008565:Membrane Proteins; D050505:Mutant Proteins; D009363:Neoplasm Proteins; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
keywords: CAMP responsive element binding protein; Gene expression; Matrix metalloproteinase-2; Nucleoplasmic Ca(2+); STIM1