Loss of STIM1 and STIM2 in Salivary Glands Disrupts ANO1 Function but Does Not Induce Sjogren's Disease.

IF 5.1 Q2 CELL BIOLOGY Function (Oxford, England) Pub Date : 2025-02-12 DOI:10.1093/function/zqae047

Ga-Yeon Son, Anna Zou, Amanda Wahl, Kai Ting Huang, Saruul Zorgit, Manikandan Vinu, Fang Zhou, Larry Wagner, Youssef Idaghdour, David I Yule, Stefan Feske, Rodrigo S Lacruz

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Abstract

Ca2+ signaling via the store-operated Ca2+ entry (SOCE) mediated by STIM1 and STIM2 proteins and the ORAI1 Ca2+ channel is important in saliva fluid secretion and has been associated with Sjogren's disease (SjD). However, there are no studies addressing STIM1/2 dysfunction in salivary glands or SjD in animal models. We report that mice lacking Stim1 and Stim2 [Stim1/2K14Cre(+)] in salivary glands exhibited reduced Ca2+ levels and hyposalivate. SOCE was functionally required for the activation of the Ca2+ activated Cl- channel ANO1. Ageing Stim1/2K14Cre(+) mice showed no evidence of lymphocytic infiltration or increased levels of autoantibodies characteristic of SjD, possibly associated with a downregulation of toll-like receptor 8 (Tlr8) expression. Salivary gland biopsies of SjD patients showed increased expression of STIM1 and TLR7/8. Our study shows that SOCE activates ANO1 function and fluid secretion in salivary glands and highlights a potential link between SOCE and TLR signaling in SjD.

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唾液腺中 STIM1 和 STIM2 的缺失会破坏 ANO1 的功能，但不会诱发 Sjogren 病。

由 STIM1 和 STIM2 蛋白及 ORAI1 Ca2+ 通道介导的贮存操作 Ca2+ 进入（SOCE）信号在唾液分泌中起着重要作用，并与 Sjogren 病（SjD）有关。然而，目前还没有针对唾液腺或 SjD 动物模型中 STIM1/2 功能障碍的研究。我们报告说，唾液腺中缺乏 Stim1 和 Stim2（Stim1/2K14Cre(+)）的小鼠表现出 Ca2+ 水平降低和唾液分泌过少。激活 Ca2+ 激活的 Cl- 通道 ANO1 在功能上需要 SOCE。老龄化的 Stim1/2K14Cre(+) 小鼠没有出现淋巴细胞浸润或 SjD 特征性自身抗体水平升高的迹象，这可能与收费样受体 8 (Tlr8) 表达下调有关。SjD患者唾液腺活检结果显示，STIM1和TLR7/8的表达增加。我们的研究表明，SOCE能激活唾液腺中的ANO1功能和液体分泌，并强调了SOCE和TLR信号在SjD中的潜在联系。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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