唾液腺におけるId4の役割とIgG4関連疾患病態形成への関与

• Published in: 日本薬理学会年会要旨集 p. 1-B-P-059
• Main Authors: 木村, 宗惟, 林, 慶和, 矢野, 恵奈, 佐伯, 彩華, 安河内, 篤, 森山, 雅文, 中村, 誠司, 自見, 英治郎, 安河内（川久保）, 友世
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2022
• Subjects: mRNA; salivary gland; その他
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.96.0_1-B-P-059

Id (inhibitor of DNA binding/differentiation), a group of dominant negative transcriptional regulators for basic helix-loop-helix transcription factors, consists of Id1-Id4. Previous studies showed Id proteins are involved in cell differentiation and proliferation, and those deficiency leads various pathological conditions. However, the physiological functions of Id4 have not been clarified. We thus investigated the role of Id4 in the salivary gland.In this study, we first analyzed the impact of Id4 on salivary glands using Id4 deficient (Id4 KO) mice. The submandibular glands (SMG) weight and saliva secretion in Id4 KO mice were significantly decreased compared to those in wild-type mice. Histological analysis revealed that increased expressions of various differentiation markers and significant mucus accumulation were observed in the SMG of Id4 KO mice. Subsequently, we investigated the possibility that Id4 is involved in human pathology, such as Sjögren syndromeand IgG4-RD in which saliva secretion often decreases. As a result, the expression level of Id4 was significantly decreased in the SMG tissue of IgG4-RD, and miRNA-mRNA integrated analysis using human samples revealed that Id4 might be downregulated by hsa-miR-486-5p in IgG4-RD salivary glands.Taken together, we suggest that Id4 is essential for the homeostasis of salivary glands, and miR-486-5p, as well as Id4, might be associated with the pathophysiology of IgG4-RD.