Free Fatty Acids Differentially Downregulate Chemokines in Liver Sinusoidal Endothelial Cells: Insights into Non-Alcoholic Fatty Liver Disease.
Free Fatty Acids Differentially Downregulate Chemokines in Liver Sinusoidal Endothelial Cells: Insights into Non-Alcoholic Fatty Liver Disease.
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DOI：
10.1371/journal.pone.0159217
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Rosen HR
中科院分区：
文献类型：
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作者：
McMahan RH;Porsche CE;Edwards MG;Rosen HR
非酒精性脂肪肝是西方世界普遍存在的问题。肝窦内皮细胞（LSEC）已被证明在肝损伤和修复中发挥重要作用，但其在非酒精性脂肪性肝病的潜在发病机制中的作用仍不清楚。在这里，我们评估了脂肪变性对非酒精性脂肪性肝病小鼠模型和永生化LSEC细胞系中LSEC基因表达的影响。使用微阵列，我们确定了不同的基因表达谱暴露于游离脂肪酸。基因通路分析显示了许多差异表达的基因，包括那些参与脂质代谢和信号传导以及炎症的基因。有趣的是，与肝细胞相反，脂肪酸导致原代和LSEC细胞系中促炎趋化因子包括CCL 2（MCP-1）、CXCL 10和CXCL 16的表达降低。趋化因子下调转化为单核细胞迁移的显著抑制，从脂肪变性肝脏中分离的LSEC表现出类似的抗炎表型转变。总的来说，这些途径可能代表了逆转与非酒精性脂肪性肝病相关的肝损伤的代偿机制。
Non-alcoholic fatty liver disease is a prevalent problem throughout the western world. Liver sinusoidal endothelial cells (LSEC) have been shown to play important roles in liver injury and repair, but their role in the underlying pathogenetic mechanisms of non-alcoholic fatty liver disease remains undefined. Here, we evaluated the effects of steatosis on LSEC gene expression in a murine model of non-alcoholic fatty liver disease and an immortalized LSEC line. Using microarray we identified distinct gene expression profiles following exposure to free fatty acids. Gene pathway analysis showed a number of differentially expressed genes including those involved in lipid metabolism and signaling and inflammation. Interestingly, in contrast to hepatocytes, fatty acids led to decreased expression of pro-inflammatory chemokines including CCL2 (MCP-1), CXCL10 and CXCL16 in both primary and LSEC cell lines. Chemokine downregulation translated into a significant inhibition of monocyte migration and LSECs isolated from steatotic livers demonstrated a similar shift towards an anti-inflammatory phenotype. Overall, these pathways may represent a compensatory mechanism to reverse the liver damage associated with non-alcoholic fatty liver disease.