Динамика печени печени плазмы фибриногена, инициирующей патогенез множественных склерозов.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
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Lin Jiaji, Han Xinyan, Zhao Chuanping, Bai Yanan, He Weitai, Liu Xiaoli, Zhao Daidi, Li Hongzeng, Guo Jun
Аннотация
Оригинал публикации
Dynamics of plasma fibrinogen unveils hepatic initiating role in the pathogenesis of multiple sclerosis.
BACKGROUND: Fibrinogen deposition in the central nervous system (CNS) is a hallmark of multiple sclerosis (MS), but its peripheral dynamics and hepatic contribution remain unclear.
METHODS: We integrated a retrospective analysis of 100 MS patients with longitudinal proteomic and transcriptomic profiling of experimental autoimmune encephalomyelitis (EAE) mice, validated by flow cytometry, western blotting, and AAV8-mediated liver-specific fibrinogen overexpression.
RESULTS: MS patients during relapse showed reduced plasma fibrinogen (2.43 ± 0.61 vs. 2.79 ± 0.60 g/L, P < 0.001) and altered hepatic indices. In EAE, fibrinogen chains and complement-coagulation cascades peaked at the pre-onset phase but declined at peak disease, coinciding with hepatic transcriptional exhaustion. Cross-tissue analysis identified hepatic activity as a major driver of plasma proteome remodeling (Variable importance in projection (VIP) = 1.32) with increased hepatic CD45⁺Ly6G⁺CD11b⁺ neutrophils. Liver-specific fibrinogen overexpression induced intrahepatic neutrophil recruitment and CNS fibrinogen deposition.
CONCLUSIONS: Hepatic fibrinogen synthesis precedes CNS deposition, revealing a liver-CNS axis in early neuroinflammation.