Project/Area Number |
16590618
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Gastroenterology
|
Research Institution | Osaka City University |
Principal Investigator |
KAWADA Norifumi Osaka City University, Graduate School of Medicine, Department of Hepatology, Associate Professor, 大学院・医学研究科, 助教授 (30271191)
|
Co-Investigator(Kenkyū-buntansha) |
IKEDA Kazuo Osaka City University, Graduate School of Medicine, Department of Anatomy, Associate Professor, 大学院・医学研究科, 助教授 (80275247)
NAKATANI Kazuki Osaka City University, Graduate School of Medicine, Department of Anatomy, Lecturer, 大学院・医学研究科, 講師 (60295699)
YOSHIZATO Katsutoshi Hiroshima University, Graduate School of Science, Professor, 大学院・理学研究科, 教授 (20095516)
OBARA Masanobu Hiroshima University, Graduate School of Science, Associate Professor, 大学院・理学研究科, 助教授 (60132479)
|
Project Period (FY) |
2004 – 2005
|
Project Status |
Completed (Fiscal Year 2005)
|
Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
|
Keywords | stellate cell / liver fibrosis / globin / heme / oxygen / myofibroblast / vitamin A / 抗ペプチド |
Research Abstract |
Cytoglobin consists of a new class of hexacoordinate globin superfamily, which was recently discovered by a proteomics approach for the rat hepatic stellate cell, an unique fibroblastic cell in the liver. Unlike hemoglobin, myoglobin and neuroglobin, cytoglobin is ubiquitously expressed in several organs including the liver, pancreas, kidney, spleen, intestine and lung, although its detailed localization is unclarified. Immunohistochemistry and immunoelectronmicroscopy revealed that cytoglobin is uniquely localized in fibroblast-like cells in splanchnic organs, namely vitamin A-storing cell lineage, but neither in epithelial cells, endothelial cells, muscle cells, blood cells, macrophages, nor dermal fibroblasts. Expression of cytoglobin was upregulated in fibrotic lesions of pancreas and kidney in which activated fibroblast-like cells or myofibroblasts increased in number. In cultured hepatic stellate cells, cytoglobin expression was augmented by the stimulation with serum, platelet-derived growth factor-BB and transforming growth factor-beta 1. These results indicate that cytoglobin is a tissue hemoglobin uniquely localized in splanchnic fibroblastic cell lineage and may play a role in fibrotic organ disorder. Additional experiments obtained by purified and crystallized cytoglobin revealed that this protein bind oxygen, nitric oxide and carbon monoxide in a manner similar to myoglobin. Thus, cytoglobin is a novel globin that play a role in oxygen transport in visceral myofibroblasts and in contrast myoglobin seems to be a muscle cell-specific oxygen carrier.
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