Chronic Treatment of Hematopoietic PGD Synthase Inhibitor Improves Skeletal Muscle Function and Cardiac Function in DMD

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293051
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: University of Tsukuba
• Principal Investigator: ARITAKE Kosuke 筑波大学, 国際統合睡眠医科学研究機構, 准教授 (70390804)
• Co-Investigator(Kenkyū-buntansha): 永田 奈々恵 筑波大学, 国際統合睡眠医科学研究機構, 研究員 (80390805)
• Co-Investigator(Renkei-kenkyūsha): URADE Yoshihiro 筑波大学, 国際統合睡眠医科学研究機構, 教授 (10201360)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: プロスタグランジンD2 / プロスタグランジンD合成酵素 / デュシェンヌ型筋ジストロフィー / 生理活性脂質 / 肥満細胞 / プロスタグランジンD合成酵素阻害薬

Outline of Final Research Achievements

We found that the hematopoietic PGD synthase (HPGDS) catalyzed PGD2 production, estimated by its urinary metabolite (tetranor-PGDM), was significantly enhanced in mdx mice, a model for DMD. We also found that HPGDS expressed on the accumulated mast cells or macrophages around the damaged muscle cells in mdx mice. Chronic treatment with an inhibitor for hematopoietic PGD synthase efficiently decreased inflammatory cell migration in muscles and grouped-necrosis of skeletal muscle, and improved the decrement of locomotor activities, and also ameliorated the isolated skeletal muscle contraction of mdx. HPGDS inhibitor treated mdx hearts were less fibrotic, reductions in left ventricular mass and ejection fraction and fractional shortening were also observed. These results demonstrate that over production of PGD2 catalyzed by HPGDS accelerate the DMD pathology and the pharmacological inhibition of hematopoietic PGD synthase might provide functional benefit to DMD patients.

Free Research Field

薬理学