Summary of Research Project Results under JSPS FY2002
"Research for the Future Program"

1.Research Institution Tokai University
2.Research Area Life Sciences
3.Research Field Genetic and Environmental Factors in Diseases Prevalent in Adults and the Elderly
4.Term of Project FY 1998 - FY 2002
5.Project Number 98L00802
6.Title of Project In Vivo Molecular Studies on Cardio-renal Remodeling

7.Project Leader
Name Institution,Department Title of Position
Iekuni, Ichikawa Tokai University, School of Medicine Professor

8.Core Members

Name Institution,Department Title of Position
Taiji, Matsusaka Tokai University, Medical Research Institute Assistant Professor
Fumio, Niimura Tokai University, School of Medicine Assistant Professor
Yoichi, Miyazaki The Jikei University, School of Medicine Assistant Researcher

9.Summary of Research Results

  Our project has pursued the in vivo roles of the renin-angiotensin system in the progression of cardiovascular and renal diseases. We have demonstrated the mode of local and systemic actions of Ang II on cardiac fibroblasts, vascular smooth muscle cells, macrophages, mesangial cells and adrenal zona glomerulosa cells, utilizing genetically engineered mice, including chimeric mice. We also demonstrated that Ang II plays an important role in the development and the function of the urinary tract.
  We aimed to clarify the role of Ang II in the evolution of glomerular sclerosis, the hallmark of the chronic renal failure. A major hurdle exists, however, due to the lack of an experimental mouse model for glomerular sclerosis. Our study aimed to generate a mouse model of glomerular sclerosis. Based on previous studies showing that podocyte injury is often associated with glomerulosclerosis, we generated a mouse model in which selective podocyte injury can be induced. After the induction of podocyte injury, the mice showed massive proteinuria and developed glomerular sclerosis.
  Thus, we found the conclusive evidence that podocyte injury is causally linked to glomerular sclerosis. This model will be a powerful tool to investigate the role of various gene products in the progression of renal diseases.

10.Key Words
(1)heart failure   (2)chronic renal failure   (3)glomerulosclerosis
(4)knockout mouse   (5)chimeric mouse   (6)bone marrow transplantation
(7)hypertension   (8)Renin   (9)Angiotensin