Regulatory mechanism of SLC26A7 and Pendrin in relation to the pathogenesis of multinodular goiter

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07451
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Kyorin University
• Principal Investigator: Kamma Hiroshi 杏林大学, 医学部, 特任教授 (10195191)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 甲状腺濾胞 / ヨ ウ 素輸送蛋白 / SLC２6 A4 / Isidrin / SLC26A4 / Pendrin / 腺腫様甲状腺腫 / ヨ ウ 素貯蔵調節

Outline of Final Research Achievements

As a result of ortholog analysis of SLC26A7 (Isidrin) and Pendrin, it was thought that Isidrin parted from Pendrin in the phylogenetic process of fish. As a result of promoter analysis, CRE sequence was found in Isidrin, and it was thought that expression of Isidrin is regulated by a cAMP signal system.
I made a specific antibody and performed an immunohistological study. In the active follicles of the Basedow's disease, the apical expression of Isidrin decreased in a follicle including the highly-concentrated thyroglobulin. In some cases of multinodular goiter, Isidrin was overexpressed in Sanderson’s pollsters, suggesting a possibility that regulatory abnormality of the iodine storage by Isidrin is associated with pathogenesis of multinodular goiter.

Free Research Field

Pathology

Academic Significance and Societal Importance of the Research Achievements

Isidrinは2019年に我々がPendrinの機能を補完する新たな甲状腺のヨウ素トランスポーターである。今回、PendrinとIsidriｎの分子系統的な違い、およびヨウ素トランスポーターが2種類ある理由をはじめて示した。Isidrinは、ヨウ素貯蔵が必要な環境で生物が生息するためにＰｅｎｄｒｉｎから分かれたこと、そしてIsidrinの発現はホルモンの機能調節機構（cAMP）の影響を強く受けることも明らかにした。新たにＩｓｉｄｒｉｎ特異的な抗体を作成し、実臨床検体の濾胞局所でのIsidrinとPendrinの発現様式の違いを明らかにし、結節性甲状腺腫の発病機序につながると考えた。