2005 Fiscal Year Final Research Report Summary
Investigation of molecular mechanism in the development of chronic obstructive pulmonary disease (COPD) and susceptibility to cigarette smoke-induced lung injury using transgenic animal models.
| Project/Area Number |
16590734
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Respiratory organ internal medicine
|
|---|
| Research Institution | Gunma University |
|---|
Principal Investigator |
SUGA Tatsuo GUNMA UNIVERSITY, ASSISTANT PROFESSOR, 医学部, 助手 (50334115)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KURABAYASHI Masahiko GUNMA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, PROFESSOR, 医学系研究科, 教授 (00215047)
NAGAI Ryozo TOKYO UNIVERSITY HOSPITAL, PROFESSOR, 医学部付属病院, 教授 (60207975)
|
|---|
| Project Period (FY) |
2004 – 2005
|
| Keywords | Animal model of chronic obstructive pulmonary disease (COPD) / klotho gene / klotho mutant mice / klotho mutant rats / pulmonary emphysema |
|---|
| Research Abstract |
1.Phenotypes of klotho transgenic rats
(1)Systolic blood pressure in transgenic rats was similar to wild-type rats.
(2)Microscopic findings showed no significant difference in the aorta, the heart, and the kidney between wild-type and transgenic rats.
(3)Endothelial-dependent relaxation of the aorta in response to acetylcholine was significantly ameliorated in transgenic rats as compared with wild-type rats.
(4)A decrease in urinary excretion of nitric oxide metabolites was observed in transgenic rats as compared to wild-type rats. Urinary excretion of isoprostane was reduced in transgenic rats as compared with wild-type rats.
(5)Hydroethidine, an oxidative fluorescent dye, was used to evaluate the level of superoxide in situ. Superoxide production is decreased in klotho transgenic rats as compared to wild-type.
2.Regulation of multiple ageing-like phenotypes by inducible klotho gene expression in klotho mutant mice
To investigate the ability of klotho gene expression to regulate the development of ageing-related disorders, we established an inducible klotho gene expression system using homozygous mutant klotho mice. Mice carrying an exogenous klotho gene fused to the mouse metallothionein-I promoter, in which klotho gene expression was dependent on zinc water feeding.
We demonstrate that many advanced ageing-like phenotypes of homozygous mutant klotho mice were restored to normal whenever klotho gene expression was induced. Conversely, decreasing klotho gene expression in these rescued homozygous mutant klotho mice induced several ageing-like phenotypes.
Our data indicate that klotho gene expression may be effective in the treatment of multiple age-related disorders and is essential for maintaining animals free of these disorders.
|
