The role of osteopontin on diabetic cardiomyopathy

2003 Fiscal Year Final Research Report Summary

• Project/Area Number: 14570676
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Nagasaki University
• Principal Investigator: ASHIZAWA Naoto Nagasaki University, Hospital of Medicine and Dentistry, Lecturer, 医学部・歯学部附属病院, 講師 (10301368)
• Co-Investigator(Kenkyū-buntansha): KAWANO Hiroaki Nagasaki University, Hospital of Medicine and Dentistry, Research Associate, 医学部・歯学部附属病院, 助手 (30325659) ; SETO Shinji Nagasaki University, Graduate School of Biomedical Sciences, Associate Professor, 大学院・歯薬学総合研究科, 助教授 (00136657) ; YANO Katsusuke Nagasaki University, Graduate School of Biomedical Sciences, Professor, 大学院・歯薬学総合研究科, 教授 (50039864) ; YAMASHITA Syunichi Nagasaki University, Graduate School of Biomedical Sciences, Professor, 大学院・歯薬学総合研究科, 教授 (30200679)
• Project Period (FY): 2002 – 2003
• Keywords: Diabetes mellitus / Osteopontin / Hypoxia / Cardiac myocyte / Cardiac fibroblast / Extracellular matrix

Research Abstract

【Aim】The effect of high glucose and hypoxia on the expression of osteopontin (OPN) in cultured neonatal cardiac myocytes and cardiac fibroblasts was examined. (Method) Quiescent culture of cardiac myocytes or cardiac fibroblasts were exposed to either normoxia (18% O_2) or hypoxia (1% O_2) in a serum-free medium with normal-glucose (NG, 5.5 mM glucose) or high glucose (HG, 35.5 mM glucose) for 2 to 24 hours, and OPN expression was assessed by RT-PCR and Western blotting. 【Results】Both cardiac myocytes and cardiac fibroblasts exposed to hypoxia under NG conditions resulted in a significant increase (x 1.5 to 2.0) in OPN mRNA levels at 2 h, followed by normoxia under HG and hypoxia under HG. At 24 h, however, the OPN mRNA expression was highest in hypoxia under HG condition in cardiac myocytes. On the other hand, at 24 h, OPN mRNA expression was elevated to an almost same extent among hypoxia under HG, hypoxia under NG and normoxia under HG condition comparing with normoxia under NG in cardiac fibroblasts. Exposure to hypoxia for 24 h on cardiac myocytes enhanced the OPN protein expression by three times regardless of glucose level. 【Conclusion】In cultured cardiac fibroblasts, hypoxia was more affected on OPN expression than high glucose. At the early stage of hypoxic condition, high glucose seemed to be beneficial by acting in cardioprotective manner.