Circadian control of ConA-induced acute liver injury and inflammatory response via Bmal1 regulation of Junb
نویسندگان
چکیده
Background & AimsThe circadian rhythms play significant roles in immune responses and many inflammatory processes liver diseases are associated with malfunctioning molecular clocks. However, the significance of clock autoimmune hepatitis (AIH) which is characterized by immune-mediated hepatocyte destruction extensive cytokine production remains unclear.MethodsWe tested difference susceptibility to injury induced Concanavalin A (ConA) at various time points throughout a day mice analyzed effects global, or myeloid cell deletion core gene, Bmal1, on responses. Multiple biology techniques macrophage-specific knockdown Junb, Bmal1 target were used investigate involvement Junb control ConA-induced hepatitis.ResultsThe highly dependent timing ConA injection. The treatment ZT0 (lights on) triggers highest mortality as well severest Further study revealed that this effect was driven macrophage, but not hepatocyte, Bmal1. Mechanistically, controls diurnal variation directly regulating transcription promoting M1 macrophage activation. Inhibition macrophages blunts administration time-dependent attenuates injury. Moreover, we demonstrated promotes inflammation AKT ERK signaling pathways.ConclusionOur findings uncover critical role Bmal1-Junb-AKT/ERK axis provide new insights into prevention AIH.
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ژورنال
عنوان ژورنال: JHEP reports
سال: 2023
ISSN: ['2589-5559']
DOI: https://doi.org/10.1016/j.jhepr.2023.100856