| Project/Area Number |
09045082
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B).
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Human pathology
|
|---|
| Research Institution | Kochi Medical School |
|---|
Principal Investigator |
ENZAN Hideaki Department of Pathology, Kochi Medical School, Professor, 医学部, 教授 (00034645)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KURODA Naoto Department of Pathology, Kochi Medical School, assistant, 医学部, 助手 (60291457)
HIROI Makoto Department of Pathology, Kochi Medical School, Associate Professor, 医学部, 助教授 (20156699)
張 愿有 佳木斯大学, 医学院, 教授
陶 富山 佳木斯大学, 医学院, 教授
中山 宏文 高知医科大学, 医学部, 助手 (50253068)
清久 泰司 高知医科大学, 医学部, 助手 (70195402)
張 憲有 佳木斯大学, 医学院, 教授
|
|---|
| Project Period (FY) |
1997 – 1999
|
| Project Status |
Completed (Fiscal Year 1999)
|
| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1997: ¥1,200,000 (Direct Cost: ¥1,200,000)
|
|---|
| Keywords | liver fibrosis / Ito cell / hepatic stellate cell / myofibroblast / TGF-β / α-smooth muscle actin / immunohistochemistry / pathology / 形質転換 / 分子生物学 / 病理学 / 免疫細胞化学 / サイトカイン |
|---|
| Research Abstract |
1. The myofibroblastic transfromation of Ito cells was a basic, but strictly localized reaction, following liver cell necrosis and appeared to be an initial and crucial event in liver fibrosis. We demonstrated, based on the extensive studies on liver morphogenesis in humans, rats and mice, that the myofibroblastic transformation of Ito cells in hepatic fibrosis of the adult may be a deviated or uncontrolled occurrence of what goes on during the fetal period.
2. Immediate]y after liver cell necrosis, adjacent Ito cells lost the topographical relationship to liver cells and sinusoidal structure. We found frequent occurrence of these "denuded" Ito cells along the margin between liver parenchyma and periportal tissue. It may be a prerequisite for the myofibroblastic transformation of Ito cells, since the neighboring fibrotic tissue contained no denuded Ito cells, but transformed Ito cells which intimately admixed with infiltrated inflammatory cells.
3. By immunohistochemistry and immunoelectron microscopy, we demonstrated the overexpression of TGF-β and its latency-associated-peptide (LAP) and also latent transforming growth factor binding protein (LTBP), not only on infiltrated inflammatory cells and macrophages, but also on proliferated bile ductular cells and transformed Ito cells themselves. Furthermore, quiescent Ito cells were positive for LTBP. These findings suggest the occurrence of paracrine activation and autocrine stimulation for Ito cell's myofibroblastic transformation in the fibrotic areas.
4. We found some liver preparations with unusual liver fibrosis among the materials from China. Through the intimate cooperation over three years, we could study human liver fibrosis a]so from the standpoint of the, geographic pathology.
Further studies on the mechanisms of TGF-β1 activation and the expression of its receptors in vivo will be necessary for a better understanding of human liver fibrosis.
|
