Transcriptional regulation of Islet-1 in tissue regeneration of Xenopus heart

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06269
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 44020:Developmental biology-related
• Research Institution: Rikkyo University
• Principal Investigator: KINOSHITA Tsutomu 立教大学, 理学部, 教授 (30161532)
• Co-Investigator(Kenkyū-buntansha): 堅田 智久 杏林大学, 医学部, 助教 (10527229)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 心筋再生 / 心筋前駆細胞 / Islet-1遺伝子 / 転写制御 / HIF1α / 種間比較

Outline of Final Research Achievements

We compared and analyzed the transcriptional regulatory mechanism of the myocardial progenitor cell regulatory gene Islet1 between Xenopus, which can regenerate myocardium even in adults, and mice, which cannot regenerate myocardium. In Xenopus, the gene expression of Islet1 and HIF1α increased on the first day after myocardial resection. The binding site of HIF1α in the transcriptional regulation of Islet1 was located in the 8th conserved region (MCR8) located upstream of the Islet1 gene. In mice and humans, the HIF1α-binding motif was lost in MCR8 region.
From these results, it is suggested that the difference between animal species in the position and direction of the HIF1α-binding motif may be the cause of the difference in the transcription function of Islet1.

Free Research Field

発生生物学

Academic Significance and Societal Importance of the Research Achievements

本研究により、心筋損傷により誘導されるHIF1αがIslet1遺伝子の転写誘導に必須であることが明らかになった。また、マウスでもカエルと同様に、心筋の損傷直後にHIF1αの発現誘導が起こるものの、HIF1αが作用すると考えられるIslet1のプロモーター領域からHIF1αの結合モチーフが欠失していることがわかった。
これらの研究結果により、哺乳動物の成体心臓にはIslet1細胞が存在しているものの、分裂能を失っている理由の一つが明らかになったといえる。これらの結果は、今後、哺乳類の心筋において組織再生への糸口を与える重要な知見と思われる。