2010 Fiscal Year Final Research Report
Development of regenerative medicine and therapeutic system for hepatic failure applied by hepatocyte nuclear factor 4
| Project/Area Number |
20590770
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Gastroenterology
|
|---|
| Research Institution | Gifu University |
|---|
Principal Investigator |
NAGAKI Masahito Gifu University, 大学院・医学系研究科, 准教授 (30293559)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
OSAWA Yosuke 岐阜大学, 大学院・医学系研究科, 助教 (60447787)
|
|---|
| Project Period (FY) |
2008 – 2010
|
| Keywords | 肝不全 / 再生医療 / 遺伝子治療 / 肝炎 / 転写因子 |
|---|
| Research Abstract |
We transfected adenovirus-mediated HNF-4 into hepatic progenitor cells, and analyzed the expressions of the liver-specific functions. Adenovirus-mediated HNF-4 gene transfer resulted in increases in the expressions of HNF-4, apolipoprotein (Apo) A1 ApoC3, and pregnane X receptor (PXR) mRNA. HNF-4-overexpressing hepatic progenitor cells were then injected into recipient mice, which were treated with dimethylnitrosamine and 30% partial hepatectomy. The treated mice survived significantly longer than the control mice. The plasma levels of albumin, total cholesterol, and glucose were higher in the mice treated with cells transfected by HNF-4 than in the control mice. Male Wistar rats were administered 2-acetylaminofluorene subcutaneously. Seven days later, they received 70% partial hepatectomy and infected with a recombinant adenovirus carrying the cDNA for HNF-4 or Lac-Z. The total numbers of oval cells significantly decreased in the HNF-4 treated rats. At this point, HNF-4-treated rats experienced an inhibition of liver cell proliferation, while mRNA expressions of HNF-4, apolipoprotein CIII, tyrosine amino transferase and albumin, markers for the differentiation of hepatocytes, increased. In contrast, mRNA expression of cytokeratin-19, a marker for the differentiation of biliary epithelial cells, decreased in the livers of HNF-4 transferred rats. These findings demonstrate that adenovirus-mediated HNF-4 transfection induces the differentiation from hepatic progenitor cells to hepatic parenchymal cells in vitro and that these cells may be useful as a source for cell transplantation in liver diseases. The transfer of HNF-4 gene could accelerate the differentiation of hepatic oval cells to hepatocytes.
|
-
-
[Journal Article] Acid sphingomyelinase regulates glucose and lipid metabolism in hepatocytes through AKT activation and AMP-activated protein kinase suppression.2011
Author(s)
Osawa Y, Seki E, Kodama Y, Suetsugu A, Miura K, Adachi M, Ito H, Shiratori Y, Banno Y, Olefsky JM, Nagaki M, Moriwaki H, Brenner DA, Seishima M.
-
Journal Title
FASEB J 25
Pages: 1133-1144
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
[Remarks] ホームページ等
