Basic studies of therapeutic modality for polycystic kidney disease explored by epigenetic modification of cellular matrix-adhesion proteins

2014 Fiscal Year Final Research Report

• Project/Area Number: 24592450
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Nara Medical University
• Principal Investigator: ISHIBASHI MIchio 奈良県立医科大学, 医学部, 研究員 (40107032)
• Co-Investigator(Kenkyū-buntansha): HIGASHIHARA Eiji 杏林大学, 医学部, 教授 (00092312) ; NAGAO Shizuko 藤田保健衛生大学, 医学部・疾患モデル教育研究センター, 准教授 (20183527) ; CHIHARA Yoshitomo 奈良県立医科大学, 医学部, 講師 (40405395) ; KOJIMA Naoto 京都薬科大学, 薬学部, 講師 (90420413)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 多発性嚢胞腎 / ＰＣＫラット / 細胞マトリックス / ベンゾイソフラノン誘導体

Outline of Final Research Achievements

We studied the mechanism of progression of polycystic kidney disease explored by the pathological pictures of PCK rat kidneys of 5-week old male, treated with Benzoisofuranone derivatives for five weeks, and the epigenetic modification of cellular matrix-adhesion protein genes such as HIF-1, Galectin-3, DNMT1, Mlana, RTL1, Gypsy integrase-1 (Gin1) in frozen PCK kidney tissues. The pathology of beneficial findings of PCK rat kidney treated, showed stabilization of ductal tubules and that of peri-ductal capillary without sludging of blood, and minimization of cystic mass growing. The response of HIF-1 mRNA expression of frozen kidney was decreased with concomitant increase of DNA methylation level, which is benefical response of anti-fibrosis of PCK kidney. An increase of mRNA expression of Mlana, having function of angiogenesis, and a decrease of that of Gin1 were observed. Those findings suggested that an epigenetic modification played a role in the progression of PCK kidneys.

Free Research Field

泌尿器科学