| Project/Area Number |
13470218
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Endocrinology
|
|---|
| Research Institution | KYOTO UNIVERSITY |
|---|
Principal Investigator |
ITOH Hiroshi Kyoto University Graduate School of Medicine, Department of Medicine and Clinical Science, Associate Professor, 医学研究科, 助教授 (40252457)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
HOSODA Kiminori Kyoto University Graduate School of Human and Environmental Studies, Assistant Professor, 人間環境学研究科, 助手 (40271598)
SUGA Shinichi National Cardiovascular Center, Department of Organogenesis, Laboratory Chief, 室長 (70273456)
OGAWA Minerato Kumamoto University Institute of Molecular Embryology and Genetics, Division of Cell Differentiation, Professor, 発生医学研究センター, 助教授 (70194454)
UMEMURA Kazuo Hamamatsu University School of Medicine, Department of Pharmacology, Professor, 医学部, 教授 (40232912)
|
|---|
| Project Period (FY) |
2001 – 2002
|
| Project Status |
Completed (Fiscal Year 2002)
|
| Budget Amount *help |
¥10,700,000 (Direct Cost: ¥10,700,000)
Fiscal Year 2002: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2001: ¥6,600,000 (Direct Cost: ¥6,600,000)
|
|---|
| Keywords | vascular hormone / natriuretic peptides / adrenomedullin / endothelial cells / vascular smooth muscle cells / vascular regeneration / ES cells / cGMP / 血管新生 / cGMP依存性プロテインキナーゼ |
|---|
| Research Abstract |
We previously demonstrated that vascular hormones secreted from endothelial cells not only regulate vascular tone but also vascular remodeling, and also reported that Flk-1, one of VEGF receptors, -positive cells derived from ES cells can be differentiated into endothelial cells and vascular smooth muscle cells (VSMC) to construct blood vessels in vitro and named them as "vascular progenitor cells (VPC)". In this research, by using several genetically-engineered mice, we revealed that activation of natriuretic peptides/cGMP/cGMP-dependent protein kinase (cGK) pathway accelerates endothelial repair to recover endothelial functions and induces vascular regeneration. Natriuretic peptides inhibit Rho activity by directly phosphorylating Ser residue of Rho in (VSMC) and activate Erk 1/2 and Akt in endothelial cells. Gene transfer of CNP, which we elucidated to act as endothelium-derived relaxing peptide, potentiated blood in hind limb-ischemia model. Implasntation of ES cell-derived VPC differentiated by VEGF into adult mice resulted in neo vessel formation to augment local blood flow.
|
