Development of the novel gene modulator PI polyamide targeting protein S as a therapeutic agent for diabetes mellitus and diabetic nephropathy

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K08737
• 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: Nihon University
• Principal Investigator: TSUNEMI Akiko 日本大学, 医学部, 研究員 (90646035)
• Co-Investigator(Kenkyū-buntansha): 上野 高浩 日本大学, 医学部, 兼任講師 (40386008) ; 阿部 雅紀 日本大学, 医学部, 教授 (70459890)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: PI ポリアミド / 糖尿病性腎症

Outline of Final Research Achievements

Pyrrole-Imidazole polyamides (PI polyamides) are chemical compounds that specifically inhibit transcription factor binding. A PI polyamide that targets mouse protein S and increases protein S gene expression was designed. Treatment of NCTC1469 cell with 1nM PI polyamide significantly increased protein S mRNA and protein expression. Sufficient effects were not observed in the blood glucose level and glucose tolerance test of diabetic mice, but in kidney tissue, it suppressed the expression of tgfb1 and CTGF mRNA, and suppressed the proliferation of mesangial cells in the glomerulus.

Free Research Field

腎臓病

Academic Significance and Societal Importance of the Research Achievements

糖尿病性腎症は透析導入原因疾患の第一位を占め、多くの医療費が投じられているが、未だ有効な治療法は確立していない。今回、プロテインSの負の転写調節領域に、PIポリアミドを設計、合成し、実験を行ったところ、培養細胞での転写活性を上昇させ、マウス腎臓での線維化に関わる遺伝子や、糸球体でのメサンギウム細胞の増殖を抑制したことにより、新たな治療薬としての可能性を示した。