Study of body fluid regulation by thyroid hormone mediated by transcriptional regulation of aquaporin 2

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08226
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Matsushita Akio 浜松医科大学, 医学部附属病院, 講師 (50402269)
• Co-Investigator(Kenkyū-buntansha): 佐々木 茂和 浜松医科大学, 医学部附属病院, 講師 (20303547)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 甲状腺ホルモン / 甲状腺ホルモン受容体 / アクアポリン2 / 抗利尿ホルモン / GATA2

Outline of Final Research Achievements

Aquaporin 2 (AQP2) is a water channel molecule expressed in renal collecting duct cells. It has been reported that the transcription factor GATA2 is important for the expression of the AQP2 gene. We examined the transcriptional activity of the AQP2 gene by expressing the thyroid hormone (T3) receptor (TR) and GATA2 in cultured kidney-derived cells. The antidiuretic hormone DDAVP enhanced GATA2-mediated transcription of AQP2, while T3 antagonized DDAVP and suppressed AQP2 transcription. Disruption of the GATA2 binding sequence on the AQP2 gene abolished the T3/TR-mediated transcriptional regulation of AQP2, while disruption of the CREB binding sequence downstream of the DDAVP signal maintained the T3/TR transcriptional regulation, confirming the importance of the interaction between GATA2 and TR.

Free Research Field

内分泌代謝内科

Academic Significance and Societal Importance of the Research Achievements

甲状腺機能低下症では、浮腫や体重増加が認められ水分貯留傾向となることが知られている。甲状腺ホルモン(T3)はGATA2との相互作用を介してAQP2の転写を抑制し利尿効果を発揮していることが考えられた。甲状腺機能低下症ではAQP2の転写抑制がなくなり、AQP2が高発現することにより抗利尿効果が強まって水分貯留傾向となるものと考えられた。