Summary of Research Project Results under JSPS FY2001
"Research for the Future Program"



1.Research Institution University of Tsukuba
 
2.Research Area Life Sciences
 
3.Research Field Genetic and Environmental Factors in Diseases Prevalent in Adults and Elderly; Molecular and Cellular Mechanism of Vascular Complications
 
4.Term of Project FY 1997 〜 FY 2001
 
5.Project Number 97L00804
 
6.Title of Project Genetic function of Molecular Network on Blood Pressure Regulation

7.Project Leader
Name Institution,Department Title of Position
Akiyoshi Fukamizu University of Tsukuba, Center for Tsukuba Advanced Research Alliance Professor

8.Core Members

Names Institution,Department Title of Position
Ken-ichi Yagami University of Tsukuba, Laboratory Animal Resource Center Professor
You Takuwa Kanazawa University, School of Medicine Professor

9.Summary of Research Results

My laboratory studies the regulated function of transcription and signal transduction and their roles in cardiovascular and brain systems. Much of the work focuses on the identification of novel genes that contribute to the homeostatic maintenance of the body, and on the creation and analyses of transgenic and knockout mice with hypertension, hypotension, or tumor transformation. A variety of molecular and cellular biological and biochemical studies underway in our laboratory concentrate upon understanding the mechanisms by which the ligand-receptor signal arrays modulate the blood-brain barrier (BBB) function and the coactivator CBP regulates the nuclear function. In this regard, we have recently revealed the impaired BBB function in angiotensinogen-deficient mice, identified a small G protein coupling with angiotensin II receptor, and succeeded in cloning a novel orphan seven-transmembrane receptor which is expressed in endothelial cells. Furthermore, we have discovered a number of leucine zipper and zinc-finger transcription factors as well as CBP-associated factors including known and novel ones, which seem to operate cardiovascular and brain cell functions. Knowledge about the regulation of ligand receptor-mediated BBB and a detailed understanding of the functional significance of the protein-protein interactions in which the zinc transcription factors or CBP-associated factors participate may ultimately provide the insights needed to develop new drugs that can be employed to either induce tumor cell death or alternatively to block cell death or to improve tissue damages in the setting of cardiovascular and neurodegenerative diseases.

10.Key Words

(1)Hypertension、(2)renin、(3)angiotensin
(4)knockout mouse、(5)transgenic mouse、(6)pregnancy-induced hypertension
(7)seven transmembrane receptor、(8)atheloscrelosis、(9)diabetes


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