CCL20 is up-regulated in non-alcoholic fatty liver disease fibrosis and is produced by hepatic stellate cells in response to fatty acid loading.
CCL20 is up-regulated in non-alcoholic fatty liver disease fibrosis and is produced by hepatic stellate cells in response to fatty acid loading.
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DOI：
10.1186/s12967-018-1490-y
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发表时间：
2018-04-24
影响因子：
7.4
通讯作者：
Gerhard GS
中科院分区：
文献类型：
--
作者：
Chu X;Jin Q;Chen H;Wood GC;Petrick A;Strodel W;Gabrielsen J;Benotti P;Mirshahi T;Carey DJ;Still CD;DiStefano JK;Gerhard GS
非酒精性脂肪性肝病（NAFLD）是极度肥胖的一种常见并发症。肝脏的脂肪负荷可以进展为炎症和纤维化，包括肝硬化。从单纯性脂肪变性到纤维化的进展中涉及的分子因素仍然知之甚少。采用微阵列、PCR阵列和RNA测序对来自极度肥胖患者肝活检组织的RNA进行基因表达谱分析。根据组织学检查结果对患者进行分组，包括正常肝组织学，无脂肪变性、小叶炎症或纤维化，以及1、2、3和4级纤维化伴脂肪变性和小叶炎症共存。使用定量PCR进行表达的验证。使用ELISA进行血清分析。采用定量PCR和ELISA在体外进行肝细胞和肝星状细胞对脂质负荷的表达分析。三种正交方法分析人肝活检RNA，每种方法都将趋化因子CCL 20（CC趋化因子配体20或MIP-3 α）基因鉴定为NAFLD纤维化中相对于正常组织学最上调的转录物之一，在复制组中得到验证。在224名NAFLD患者中测量的血清中的CCL 20蛋白水平在严重纤维化中增加（p < 0.001），肝转录物水平和血清水平中度相关。在LX-2肝星状细胞中，响应于脂肪酸加载，CCL 20的表达显著增加（p < 0.001），而不是其同源受体CC趋化因子受体6的表达，相对增加大于HepG 2肝细胞中的相对增加。这些结果表明，在NAFLD纤维化中，重要的炎症介质CCL 20的表达增加。CCL 20作为未成熟树突状细胞的化学引诱物分子，其已被证明产生许多介导肝纤维化的炎性分子。这些数据还指出肝星状细胞作为一种关键的细胞类型，可能会响应肝脏的脂质负荷。本文的在线版本（10.1186/s12967-018-1490-y）包含补充材料，可供授权用户使用。
Nonalcoholic fatty liver disease (NAFLD) is a prevalent complication of extreme obesity. Loading of the liver with fat can progress to inflammation and fibrosis including cirrhosis. The molecular factors involved in the progression from simple steatosis to fibrosis remain poorly understood. Gene expression profiling using microarray, PCR array, and RNA sequencing was performed on RNA from liver biopsy tissue from patients with extreme obesity. Patients were grouped based on histological findings including normal liver histology with no steatosis, lobular inflammation, or fibrosis, and grades 1, 2, 3, and 4 fibrosis with coexistent steatosis and lobular inflammation. Validation of expression was conducted using quantitative PCR. Serum analysis was performed using ELISA. Expression analysis of hepatocytes and hepatic stellate cells in response to lipid loading were conducted in vitro using quantitative PCR and ELISA. Three orthogonal methods to profile human liver biopsy RNA each identified the chemokine CCL20 (CC chemokine ligand 20 or MIP-3 alpha) gene as one of the most up-regulated transcripts in NAFLD fibrosis relative to normal histology, validated in a replication group. CCL20 protein levels in serum measured in 224 NAFLD patients were increased in severe fibrosis (p < 0.001), with moderate correlation of hepatic transcript levels and serum levels. Expression of CCL20, but not its cognate receptor CC chemokine receptor 6, was significantly (p < 0.001) increased in response to fatty acid loading in LX-2 hepatic stellate cells, with relative increases greater than those in HepG2 hepatocyte cells. These results suggest that expression of CCL20, an important inflammatory mediator, is increased in NAFLD fibrosis. CCL20 serves as a chemoattractant molecule for immature dendritic cells, which have been shown to produce many of the inflammatory molecules that mediate liver fibrosis. These data also point to hepatic stellate cells as a key cell type that may respond to lipid loading of the liver. The online version of this article (10.1186/s12967-018-1490-y) contains supplementary material, which is available to authorized users.
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影响因子：
5.6
作者：
Kanuri G;Bergheim I
通讯作者：
Bergheim I
影响因子：
2.9
作者：
Petrick A;Benotti P;Wood GC;Still CD;Strodel WE;Gabrielsen J;Rolston D;Chu X;Argyropoulos G;Ibele A;Gerhard GS
通讯作者：
Gerhard GS
影响因子：
4.1
作者：
Miller, Michael H.;Walsh, Shaun V.;Dillon, John F.
通讯作者：
Dillon, John F.
影响因子：
3.5
作者：
Pirazzi C;Valenti L;Motta BM;Pingitore P;Hedfalk K;Mancina RM;Burza MA;Indiveri C;Ferro Y;Montalcini T;Maglio C;Dongiovanni P;Fargion S;Rametta R;Pujia A;Andersson L;Ghosal S;Levin M;Wiklund O;Iacovino M;Borén J;Romeo S
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Romeo S
影响因子：
13.5
作者：
Bruschi, Francesca Virginia;Claudel, Thierry;Trauner, Michael
通讯作者：
Trauner, Michael