Calcium response via CRAC channels in human synovial cells induced by shear stress in rheumatoid arthritis.

IF 3.2 4区医学 Q2 PHYSIOLOGY Journal of Physiological Sciences Pub Date : 2025-07-01 Epub Date: 2025-03-06 DOI:10.1016/j.jphyss.2025.100013

Yu Okumura, Kanya Honoki, Yasuhito Tanaka, Miyako Takaki, Keiji Asada

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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.

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类风湿性关节炎中剪切应力诱导滑膜细胞通过CRAC通道的钙反应。

钙释放活化钙通道（CRAC）抑制剂在类风湿关节炎（RA）发病机制中的作用尚不清楚。我们关注参与CRAC激活的基质相互作用分子1 （STIM1）和Ca2+释放激活通道调节剂2a (CRACR2A)，以了解人RA成纤维细胞样滑膜（FLS）细胞响应剪切应力（SS）的信号传导机制。研究了人正常细胞和RA FLS细胞的培养。细胞内钙释放速率和细胞外钙内流速率对SS的响应不同，并分析了对第一和第二刺激的反应。在RA FLS细胞中，与正常细胞相比，CRAC抑制剂显著降低了第二/第一刺激比，并且与正常FLS细胞相比，STIM1和CRACR2A的表达水平显著升高。因此，FLS细胞中STIM1和CRACR2A的表达和Ca2+内流与RA的发病机制有关。

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来源期刊

Journal of Physiological Sciences 医学-生理学

CiteScore

4.40

自引率

4.30%

发文量

审稿时长

6-12 weeks

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. Fields covered: 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.