Macrophage-Specific Hypoxia-Inducible Factor-1α Contributes to Impaired Autophagic Flux in Nonalcoholic Steatohepatitis

巨噬细胞特异性缺氧诱导因子-1α导致非酒精性脂肪性肝炎自噬通量受损

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作者:Xiaojing Wang, Marcelle de Carvalho Ribeiro, Arvin Iracheta-Vellve, Patrick Lowe, Aditya Ambade, Abhishek Satishchandran, Terence Bukong, Donna Catalano, Karen Kodys, Gyongyi Szabo

Conclusion

Palmitic acid impairs autophagy via HIF-1α activation in macrophages. HIF-1α and impaired autophagy are present in NASH in vivo in mouse macrophages and in human blood monocytes. We identified that HIF-1α activation and decreased autophagic flux stimulate inflammation in macrophages through upregulation of NF-κB activation. These results suggest that macrophage activation in NASH involves a complex interplay between HIF-1α and autophagy as these pathways promote proinflammatory overactivation in MCD diet-induced NASH.

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