Abstract:
Non-alcoholic fatty liver disease (NAFLD) is a multifactorial condition characterized from hypertriglyceridemia and hepatic fat accumulation, in the absence of alcohol intake. NAFLD starts as steatosis (NAFL), and the continued injury relative to the toxic fat induces inflammation, steatohepatitis (NASH), and HCC. One of the factors determining liver degeneration during the evolution of NAFLD is a modification of Wnt/Frizzled (FZD) signaling. In particular, an inhibition of Wnt signaling and an overexpression of a specific FZD receptor protein, namely, the FZD7, have been observed in NAFLD. Actually, the prognosis and the follow-up of NAFLD is not easy, and the liver biopsy is the gold standard for an accurate detection of liver fibrosis. In this study, the modulation of the FZD7 expression levels in plasma-derived exosomes of NAFLD-affected patients, before and after specific lifestyle interventions, were experimentally evaluated by Western blotting analysis. The experimental data were analyzed by an accurate statistical study that indicated, in the exosomes derived from plasma of NAFLD patients with moderate or severe steatosis, an average expression level of FZD7 that was significantly higher than healthy subjects at baseline; conversely, the values were normalized after 90 days of specific lifestyle interventions. The overall results suggested that the FZD7 delivered by exosomes represents a good candidate as a new and effective biomarker for diagnosis and prognosis of NAFLD.
摘要:
非酒精性脂肪性肝病(NAFLD)是一种多因素疾病,其特征是高甘油三酯血症和肝脏脂肪积累,在没有酒精摄入的情况下。NAFLD开始为脂肪变性(NAFL),与有毒脂肪相关的持续损伤会引起炎症,脂肪性肝炎(NASH),和HCC。在NAFLD的进化过程中决定肝变性的因素之一是Wnt/Frizzled(FZD)信号传导的修饰。特别是,Wnt信号的抑制和特定FZD受体蛋白的过表达,即,在NAFLD中观察到FZD7。事实上,NAFLD的预后和随访不容易,肝活检是准确检测肝纤维化的金标准。在这项研究中,NAFLD患者血浆来源的外泌体中FZD7表达水平的调节,在特定的生活方式干预之前和之后,通过Western印迹分析进行实验评估。通过准确的统计研究分析了实验数据,在来自中度或重度脂肪变性的NAFLD患者血浆的外泌体中,基线时FZD7的平均表达水平显著高于健康受试者;相反,在特定的生活方式干预90天后,这些值恢复正常.总体结果表明,通过外泌体递送的FZD7代表了作为NAFLD诊断和预后的新的有效生物标志物的良好候选者。