重游的 Mallory-Denk 身体致病

• 作者: Barbara A French Fawzia Bardag-Gorce Joan Oliva Samuel W French
• 来源期刊: 世界肝病学杂志：英文版（电子版）
• 学科: 医学
• 关键词: TOLL-LIKE receptor PROINFLAMMATORY Methyl DONORS EPIGENETIC processes Drug toxicity 26s PROTEASOME IMMUNOPROTEASOME
• 年，卷（期）: 2010,（8）
• 页码范围: 295-301
• 页数: 7页
• 分类号: R363

摘要

This editorial reviews the recent evidence showing that Mallory-Denk bodies(MDBs)form in hepatocytes as the result of a drug-induced shift from the 26s proteasome formation to the immunoproteasome formation.The shift is the result of changes in gene expression induced in promoter activation,which is induced by the IFNγ and TNFa signaling pathway.This activates TLR 2 and 4 receptors.The TLR signaling pathway stimulates both the induction of a cytokine proinflammatory response and an up regulation of growth factors.The MDB-forming hepatocytes proliferate as a result of the increase in growth factor expression by the MDBforming cells,which selectively proliferate in response to drug toxicity.All of these mechanisms are induced by drug toxicity,and are prevented by feeding the methyl donors SAMe and betaine,supporting the epigenetic response of MDB formation.