|Budget Amount *help
¥3,000,000 (Direct Cost : ¥3,000,000)
Fiscal Year 1999 : ¥1,300,000 (Direct Cost : ¥1,300,000)
Fiscal Year 1998 : ¥1,700,000 (Direct Cost : ¥1,700,000)
We previously demonstrated that α-smooth muscle actin (ASMA) is a useful phenotypic marker for both normal and transformed Ito cells in the adult human liver. In this study, we examined the mechanism of myofibroblastic transformation of Ito cells in human fibrotic livers and obtained the following results ;
1. In almost all types of liver fibrosis, such as hepatitic, posthepatitic, postnecrotic, alcoholic, cardiac and biliary fibrosis, the Ito cells in the areas of liver cell necrosis were always activated. They were swollen, proliferated actively and exhibited myofibroblastic transformation which were easily identified by the cytoplasmic overexpression of ASMA. These transformed Ito cells produced large amounts of collagen and other components of extracellular matrix, while the portal fibroblasts were not significantly associated with the development of liver fibrosis.
2. The myofibroblastic transformation of Ito cells was a basic, but strictly localized reaction following liver cell necrosis and appeared to be an initial and key event in liver fibrosis.
3. By innunohistochemistry and immunoelectron microscopy, we clear]y demonstrated the localization of transforming growth factor-β (TGF-β) and its latency-associated-peptide (LAP) and latent transforming growth factor binding protein (LTBP) in fibrotic human liver tissues, suggesting the close association of myofibroblastic transformation of Ito cells with the secretion of TGF-β and its activation.
Further studies are necessary to elucidate of the mechanism of TGF-βl activation in vivo and the analysis of its receptor's expression.