Iron-rich Kupffer cells exhibit phenotypic changes during the development of liver fibrosis in NASH

• DOI: 10.1016/j.isci.2020.102032
• Publication Date: 2021-01-10T14:19:35Z
• Authors: Yohei Kanamori; Miyako Tanaka; Michiko Itoh; Kozue Ochi; Ayaka Ito; Isao Hidaka; Isao Sakaida; Yoshihiro Ogawa; Takayoshi Suganami
• Keywords: Kupffer cell

Although recent evidence suggests the involvement of iron accumulation in pathogenesis nonalcoholic steatohepatitis (NASH), underlying mechanisms remain poorly understood. Previously, we reported a unique histological structure termed "crown-like (CLS)," where liver-resident macrophages (Kupffer cells) surround dead hepatocytes, scavenge their debris, and induce inflammation fibrosis NASH. In this study, using magnetic column separation, show that iron-rich Kupffer cells exhibit proinflammatory profibrotic phenotypic changes during development NASH, at least partly, through activation MiT/TFE transcription factors. Activation factors is observed forming CLSs murine human Iron chelation effectively attenuates liver NASH model. This study provides insight into pathophysiologic role Our data also shed light on macrophage subset rich contributes to CLS formation serves as driver fibrosis.