Fc gamma RIIb expression levels in human liver sinusoidal endothelial cells during progression of non-alcoholic fatty liver disease
Fc gamma RIIb expression levels in human liver sinusoidal endothelial cells during progression of non-alcoholic fatty liver disease
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DOI：
10.1371/journal.pone.0211543
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发表时间：
2019-01-29
期刊：
影响因子：
3.7
通讯作者：
Fujiwara, Yoko
中科院分区：
文献类型：
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作者：
Ishikawa, Tomoko;Yokoyama, Hiroshi;Fujiwara, Yoko
肝窦内皮细胞（Liver sinusoidal endothelial cells，LSECs）在肝脏功能和内环境稳定中起着关键作用。LSEC功能障碍已被认为与各种肝脏疾病密切相关，包括非酒精性脂肪性肝炎（NASH），但对NASH期间LSEC中清道夫受体的命运知之甚少。Fc γ受体IIb（Fc γ RIIb），已知为清道夫受体，有助于受体介导的内吞作用和免疫复合物清除。在这项研究中，为了阐明Fc γ RIIb在非酒精性脂肪性肝病（NAFLD）进展中的命运，我们通过免疫组化检测了NAFLD活检标本中的Fc γ RIIb水平，并研究了其与NASH生物学指标和临床病理学评分恶化的相关性。Fc γ RIIb表达水平与血脂（甘油三酯、总胆固醇、高密度脂蛋白-胆固醇）、4型胶原和透明质酸的血清水平呈显著负相关，它们分别参与肝脏脂质代谢紊乱、纤维化和炎症。然而，在NAFLD的病理分级之间，Fc γ RIIb表达水平没有显著差异。在NAFLD进展过程中，炎症和纤维化可能影响Fc γ RIIb的表达及其清除功能，以维持肝脏稳态。
Liver sinusoidal endothelial cells (LSECs) play a pivotal role in hepatic function and homeostasis. LSEC dysfunction has been recognized to be closely involved in various liver diseases, including non-alcoholic steatohepatitis (NASH), but not much is known about the fate of the scavenger receptors in LSECs during NASH. Fc gamma receptor IIb (Fc gamma RIIb), known as a scavenger receptor, contributes to receptor-mediated endocytosis and immune complexes clearance. In this study, to elucidate the fate of Fc gamma RIIb in the progression of non-alcoholic fatty liver disease (NAFLD), we examined Fc gamma RIIb levels in NAFLD biopsy specimens by immunohistochemistry, and investigated their correlation with the exacerbation of biological indexes and clinicopathological scores of NASH. The Fc gamma RIIb expression levels indicated significant negative correlations with serum levels of blood lipids (triglyceride, total cholesterol, high-density lipoprotein-cholesterol), type 4 collagen and hyaluronic acid, which are involved in hepatic lipid metabolism disorder, fibrosis, and inflammation, respectively. However, there was no significant difference of Fc gamma RIIb expression levels among the pathological grades of NAFLD. During NAFLD progression, inflammation and fibrosis may influence the expression of Fc gamma RIIb and their scavenger functions to maintain hepatic homeostasis.