引用

自噬损伤与肝损伤有关。LPS刺激tlr4可上调肝细胞的自噬，但其信号通路仍不明确。本研究的目的是确定导致脂多糖刺激肝细胞自噬的信号通路。野生型肝脏细胞裂解物(WT;收集给予LPS (5 mg/kg-IP)的C57BL/6小鼠和LPS (100 ng/mL)处理24 h的WT、TLR4ko和MyD88ko小鼠的肝细胞。采用免疫印迹法、免疫荧光法、qPCR法检测LC3II、p62/SQSTM1、Nrf2、beclin1水平。通过gfp - lc3 -点状蛋白的形成和lc3ii -表达来检测自噬样激活。使用siRNA敲除Beclin1、Nrf2、p62、MyD88和TIRAP。LPS后lc3ii在肝脏和肝细胞中的表达均增加，且依赖于TLR4。肝细胞中Beclin1的表达在LPS后没有增加，而Beclin1的敲除不影响LC3II水平。 In hepatocytes given LPS, expression of p62 increased and p62 colocalized with LC3. p62-knockdown prevented LC3II puncta formation. LPS-induced LC3II/p62-puncta also required MyD88/TIRAP signaling and localization of both Nrf2 and NF B transcription factors to the nucleus to upregulate p62-expression. Therefore, TLR4-activation by LPS in hepatocytes induces a p62-mediated, not beclin1-mediated, autophagy-like clearance pathway that is hepatoprotective by clearing aggregate-prone or misfolded proteins from the cytosol and preserving energy homeostasis under stress.