The Roles of Fat-Storing Cells and TGFβ Polypeptides in Periductular Fibrosis in Fulminant Hepatitis
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The present study examines the roles of fat-storing cells and TGF β in the process of ongoing periductular fibrosis that occurs during the course of fulminant hepatitis. Hepatic specimens were obtained at autopsy from 23 patients with fulminant hepatitis. Immunohistochemistry was performed using antibodies to alpha smooth muscle actin (α SMA), proliferating cell nuclear antigen (PCNA), and transforming growth factor beta (TGF α) 1 and 2. Seven cases were examined by electron microscopy to identify the fibrogenic cells surrounding the bile ductules. The proliferated bile ductules were surrounded by spindle shaped mesenchymal cells showing positive immunoreactivity for cytoplasmic α SMA and nuclear PCNA, and the extent of periductular fibrosis was correlated with the time course of the disease. Electron microscopy confirmed these cells as fat-storing cells. Ductular epithelia maintained positive immunoreactivity for TGF β1 and 2 throughout the course of the disease, macrophages were positive for TGF β only in the earlier phase and fat-storing cells were positive in the latter phase of the disease. The process of periductular fibrosis that occurs during fulminant hepatitis is proposed to occur as follows: firstly, bile ductular proliferation appears as a reaction to massive hepatic necrosis: secondly; TGF β1 and 2 expressions in ductular epithelia and TGF β1 expression in macrophages promote the aggregation and fibrogenesis of fat-storing cells around the periductular areas; and finally, TGF β1 expression in the fat-storing cell itself additionally promotes an ongoing periductular fibrosis.
- 昭和大学・昭和医学会の論文
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