YAMAMOTO Naritaka Kyoto University Medicine Assistant Professor, 医学研究科, 助手 (30253298)
YAMAOKA Yoshio Kyoto University Medicine Professor (Chairman), 医学研究科, 教授 (90089102)
KAWADA Norihumi Osaka City University, Medicine, Assistant Professor, 医学部, 助手 (30271191)
IIMURO Yuji Kyoto University Medicine Assistant Professor, 医学研究科, 助手 (30252018)
|Budget Amount *help
¥12,000,000 (Direct Cost: ¥12,000,000)
Fiscal Year 2000: ¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1999: ¥6,000,000 (Direct Cost: ¥6,000,000)
(1) SIGNIFICANCE OF TYPE IV COLLAGEN IN LIVER SURGERY FOR PATIENTS WITH CHRONIC LIVER INJURY: Type IV collagen (IV-Col) was measured perioperatively in patients with and without chronic liver damage. It was significantly elevated in cases with liver cirrhosis. In patients with liver cirrhosis, the postoperative serum IV-Col level significantly increased as compared to cases with normal liver and chronic hepatitis. Postoperative liver failure occurred at 0%, 11.6%, and 44.4% in cases with preoperative serum IV-Col levels of 150>, 150-300, and >300 ng/ml, respectively. In cases with postoperative liver failure, serum IV-Col levels were significantly higher both pre-and postoperatively as compared to those of uneventful cases. IV-Col revealed to be an independent risk factor for postoperative liver failure.
(2) NAC (N-ACETYL CYSTEINE) SUPPRESSED PROLIFERATION OF HEPATIC STELLATE CELL AND LIVER FIBROSIS: NAC dose-dependently blocked PDGF-induced DNA synthesis and signal transduction, includ
ing MAPK and Akt, inprimary-cultured hepatic stellate cell. In vitro degradation assay with various protease inhibitors showed that reducing agents, including NAC, enhanced the catalytical activity of cathepsin B and triggered extracellular proteolysis of PDGFR, thereby leading to desensitization of the cell to PDGF-BB. Moreover, western blot showed that hepatic stellate cell secreted mature-cathepsin B into the culture medium, while vascular smooth muscle cell did not secrete cathepsin B. This nechanism was demonstrated in in vivo liver fibrosis models.
(3) HEPATIC STELLATE CELLS REGULATE PROLIFERATION OF HEPATOCYTES lEffect of stellate cells (HSC) on proliferation of hepatocytes was investigated using co-culture models. When co-cultured with HSC, hepatocyte DNA synthesis was enhanced. HGF produced by HSC seemed to be the primary factor to enhance hepatocyte proliferation. The action of HGF was augmented by extracellular matrix. The contact of HSC with hepatocyte attenuated the enhanced proliferation of hepatocyte, in which gap junction seemed also to regulate proliferation of hepatocyte. Less