Project/Area Number |
17390219
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Gastroenterology
|
Research Institution | Kagoshima University |
Principal Investigator |
TSUBOUCHI Hirohito Kagoshima University, Graduate School of Medical and Dental Sciences, Professor, 大学院医歯学総合研究科, 教授 (60145480)
|
Co-Investigator(Kenkyū-buntansha) |
OKETANI Makoto Kagoshima University, Medical and Dental Hospital., Assistant Professor, 医学部・歯学部附属病院, 講師 (50274816)
UTO Hirofumi Kagoshima University, Graduate School of Medical and Dental Sciences., Assistant Professor, 大学院医歯学総合研究科, 講師 (20347058)
HASUIKE Satoru University of Miyazak, Faculty of Medicine., Research Associate, 医学部, 助手 (50381067)
|
Project Period (FY) |
2005 – 2006
|
Project Status |
Completed (Fiscal Year 2006)
|
Budget Amount *help |
¥15,500,000 (Direct Cost: ¥15,500,000)
Fiscal Year 2006: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 2005: ¥11,100,000 (Direct Cost: ¥11,100,000)
|
Keywords | hepatocyte growth factor (HGF) / transcriptome / proteome / microanay / SELDI TOF / MS / ClinProt / fulminant hepatic failure / recombinant human HGF / HGF / SELDIプロテインチップ |
Research Abstract |
The repair of tissue injuries is a tightly regulated process involving epithelial restitution, cell proliferation, and the maturation of epithelial cells. Once tissue injury occurs, the expression of numerous growth factors and cytokines, including hepatocyte growth factor (HGF), are induced in the injured tissue. In addition to promoting hepatocyte proliferation, HGF also modulates intestinal epithelial cell proliferation and migration, leading to the acceleration of tissue repair. Additionally, HGF protects cells from apoptosis in an mal models of hepatic failure and reduces disease severity in several animal models of inflammatory bowel disease. Recently, recombinant human HGF has begun to be used to treat patients with fulminant hepatic failure. Although HGF could potentially be an important new treatment modality that promotes tissue repair in patients with various diseases, including fulminant hepatic failure and inflammatory bowel disease, additional preclinical biological studies are required. In this project, we have investigated the molecular mechanisms downstream of HGF using transcriptomics and proteomics. We used oligonucleotidc microarray analysis to identify the HGF target genes that are involved in its antiapoptotic activity. In addition, we attempted to detect proteins in serum that were associated with HGF using surface-enhanced laser desorption ionization-time of flight/mass spectrometry (SELDI-TOF/MS). Several serum proteins that showed significantly different levels in patients with fulminant hepatic failure and in healthy subjects were identified. In conclusion, this project demonstrates that transcriptomic and proteomic analyses of liver tissue and serum, respectively, are useful for examining the molecular mechanisms downstream of HGF.
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