Mechanism of hepatocyte proliferation through vascular mediators secreted by sinusoidal endothelial cells
| Project/Area Number |
04670411
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Gastroenterology
|
|---|
| Research Institution | University of Tokyo |
|---|
Principal Investigator |
HASHIMOTO Naoaki Faculty of Med.Dept of Med(I), University of Tokyo Assistant Professor, 医学部(付属病院), 助手 (00167579)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
MIESUI Hiroshi Faculty of Med, Dept of Med(I), University of Tokyo Senior Resident, 医学部(付属病院), 医員
YAMADA Haruki Faculty of Med.Dept of Med(I), University of Tokyo Assistant Professor, 医学部(付属病院), 助手 (70174729)
|
|---|
| Project Period (FY) |
1992 – 1993
|
| Project Status |
Completed (Fiscal Year 1993)
|
| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1993: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1992: ¥1,500,000 (Direct Cost: ¥1,500,000)
|
|---|
| Keywords | sinusoidal endothelial cells / vascular mediators / hepatocyte proliferation / regulation of growth / prostanoid / prostaglandor / receptor / エンドセリン |
|---|
| Research Abstract |
Vascular endothelial cells secretes various chemical mediators, and thus they control the function of various cells around them. Liver is characterized by a unique structure named sinusoids, where hepatocytes and sinusoidal endothelial cells face directly across Disse spaces. We thought that this structure was suitable for liver regeneration ; unique physiological function of the liver. We hypothesized that sinusoidal endothelial cells would regulate the proliferation of hepatocytes through secretion of vascular mediators.
We first established the primary culture system for rat sinusoidal endothelial cells, and compared them with bovine carotide endothelial cells, widely used cell priparation for experimental research of this field. Both cells secreted endothelin, typical vascular mediator, although there was difference in secreted amount. Main prostanoid they secreted were PGE2 and PGI2, respectively. PGE2 secretion of sinusoidal endothelial cells was regulated by extracellular ATP through purinergic receptors. The profile of prostanoid secreted by sinusoidal endothelial cells was diffrent from that by Kupffer cells. PGE2 was the main prostanoid that stimulated DNA systhesis of cultured hepatocytes in the presence of insulin and EGF.It acted through PGE2 receptor, which was coupled with inhibitory G protein suppressed by pertussis toxin. This suggested that the receptor was EP3 subtype, which was confirmed by examining the expression of mRNA on this subtype with mutagenic RT-PCR method.
These findings seems to support our hypothesis, and were pulished in literature as listed in the other page.
|
Report
(3 results)
Research Products
(21 results)
