Id4 modulates salivary gland homeostasis and its expression is downregulated in IgG4-related disease via miR-486-5p
Id4 modulates salivary gland homeostasis and its expression is downregulated in IgG4-related disease via miR-486-5p
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Id4 调节唾液腺稳态，其表达在 IgG4 相关疾病中通过 miR-486-5p 下调
DOI：
10.1016/j.bbamcr.2022.119404
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Kawakubo-Yasukochi T.
中科院分区：
文献类型：
--
作者：
1.Hayashi Y;Kimura S;Yano E;Yoshimoto S;Saeki A;Yasukochi A;Hatakeyama Y;Moriyama M;Nakamura S;Jimi E;Kawakubo-Yasukochi T.
唾液腺在生理上受到细胞分化、增殖、凋亡以及上皮细胞、间质内皮细胞和神经元细胞之间相互作用的协调平衡的协调，它们是Sjögren综合征（SS）或igg4相关疾病（IgG4-RD）的常见表现部位。然而，唾液腺稳态及其在这些疾病中的作用知之甚少。DNA结合/分化抑制剂4 （Inhibitor of DNA binding/differentiation 4, Id4）是一种DNA蛋白，参与许多生物事件的转录控制，包括分化。对id4缺陷小鼠的研究表明，与野生型小鼠相比，id4缺陷小鼠的下颌下腺更小，分化速度更快。此外，在缺乏Id4的情况下，也观察到口干症状和脾细胞中Th17的扩增。此外，与健康对照组相比，IgG4-RD患者唾液腺中的Id4水平显著降低，而SS患者则没有。miRNA-mRNA整合分析表明，miR-486-5p在IgG4-RD患者中上调，并可能调节病变部位的Id4。总之，这些结果为Id4在唾液分化中的抑制作用以及Id4下调与IgG4-RD之间的关键关联提供了证据。
Salivary glands are physiologically orchestrated by the coordinated balance between cell differentiation, proliferation, apoptosis, and interactions between epithelial, mesenchymal endothelial, and neuronal cells, and they are frequent sites of manifestations of Sjögren's syndrome (SS) or IgG4-related disease (IgG4-RD). However, little is known about salivary gland homeostasis and its involvement in those diseases. Inhibitor of DNA binding/differentiation 4 (Id4) is an Id protein involved in the transcriptional control of many biological events, including differentiation. Studies of Id4-deficient mice revealed that Id4-deficient submandibular glands were smaller and exhibited accelerated differentiation, compared with those from wild-type littermates. In addition, dry mouth symptoms and Th17 expansion in splenocytes were also observed in the absence of Id4. Furthermore, Id4 levels in the salivary glands of patients with IgG4-RD, but not SS, were significantly decreased compared with those of healthy controls. miRNA-mRNA integrated analysis demonstrated that miR-486-5p was upregulated in IgG4-RD patients and that it might regulate Id4 in the lesion sites. Together, these results provide evidence for the inhibitory role of Id4 in salivary differentiation, and a critical association between Id4 downregulation and IgG4-RD.