{"title":"Calcium response via CRAC channels in human synovial cells induced by shear stress in rheumatoid arthritis.","authors":"Yu Okumura, Kanya Honoki, Yasuhito Tanaka, Miyako Takaki, Keiji Asada","doi":"10.1016/j.jphyss.2025.100013","DOIUrl":null,"url":null,"abstract":"<p><p>The role of calcium release-activated calcium channel (CRAC) inhibitors in the pathogenesis of rheumatoid arthritis (RA) is unclear. We focused on stromal interaction molecule 1 (STIM1) and Ca<sup>2+</sup> release-activated channel regulator 2 A (CRACR2A), which participate in CRAC activation, to understand the signaling mechanism of human RA fibroblast-like synovial (FLS) cells in response to shear stress (SS). Human normal and RA FLS cell cultures were studied. The rates of intracellular calcium release and extracellular calcium influx in response to SS differed, and the responses to the first and second stimuli were analyzed. In the RA FLS cells, CRAC inhibitor significantly decreased the second/first stimulus ratio compared with that of the normal cells, and STIM1 and CRACR2A exhibited significantly increased expression levels compared with those in the normal FLS cells. Therefore, STIM1 and CRACR2A expression and Ca<sup>2+</sup> influx in FLS cells are implicated in the pathogenesis of RA.</p>","PeriodicalId":16832,"journal":{"name":"Journal of Physiological Sciences","volume":"75 2","pages":"100013"},"PeriodicalIF":2.6000,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957775/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Physiological Sciences","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jphyss.2025.100013","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHYSIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
The role of calcium release-activated calcium channel (CRAC) inhibitors in the pathogenesis of rheumatoid arthritis (RA) is unclear. We focused on stromal interaction molecule 1 (STIM1) and Ca2+ release-activated channel regulator 2 A (CRACR2A), which participate in CRAC activation, to understand the signaling mechanism of human RA fibroblast-like synovial (FLS) cells in response to shear stress (SS). Human normal and RA FLS cell cultures were studied. The rates of intracellular calcium release and extracellular calcium influx in response to SS differed, and the responses to the first and second stimuli were analyzed. In the RA FLS cells, CRAC inhibitor significantly decreased the second/first stimulus ratio compared with that of the normal cells, and STIM1 and CRACR2A exhibited significantly increased expression levels compared with those in the normal FLS cells. Therefore, STIM1 and CRACR2A expression and Ca2+ influx in FLS cells are implicated in the pathogenesis of RA.
期刊介绍:
The Journal of Physiological Sciences publishes peer-reviewed original papers, reviews, short communications, technical notes, and letters to the editor, based on the principles and theories of modern physiology and addressed to the international scientific community. All fields of physiology are covered, encompassing molecular, cellular and systems physiology. The emphasis is on human and vertebrate physiology, but comparative papers are also considered. The process of obtaining results must be ethically sound.
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Adaptation and environment
Autonomic nervous function
Biophysics
Cell sensors and signaling
Central nervous system and brain sciences
Endocrinology and metabolism
Excitable membranes and neural cell physiology
Exercise physiology
Gastrointestinal and kidney physiology
Heart and circulatory physiology
Molecular and cellular physiology
Muscle physiology
Physiome/systems biology
Respiration physiology
Senses.