PDF(Pubmed)
Abstract：
Forkhead box A1 (FOXA1) plays an important role in the central nervous system, and its loss can lead to the downregulation of tyrosine hydroxylase, which directly affects the synthesis of dopamine, thus leading to Parkinson\'s disease (PD). The present study aimed to explore the specific role of FOXA1 in PD. Blood samples from patients with PD were collected to determine the expression levels of FOXA1 using reverse transcription-quantitative PCR (RT-qPCR). In addition, mouse dopaminergic neuron MES23.5 cells were induced with 6-hydroxydopamine (6-OHDA) to construct an in vitro PD model in order to study the effect of FOXA1 overexpression on cell inflammation, oxidative stress and apoptosis with RT-qPCR, assay kits and TUNEL assays, respectively. Subsequently, the expression of FOXA1 was silenced to assess the effect on the downstream mechanism. The results revealed that the expression level of FOXA1 was downregulated in patients with PD, and FOXA1 overexpression attenuated 6-OHDA-induced inflammation, oxidative stress and apoptosis in MES23.5 cells. Furthermore, FOXA1 could bind to the trefoil factor 1 (TFF1) promoter, and the effects of FOXA1 overexpression on cells were reversed by TFF1 silencing, indicating that TFF1 mediated the mechanism of FOXA1 overexpression in MES23.5 cells. In conclusion, following FOXA1 transcription, TFF1 expression was activated, thereby relieving 6-OHDA-induced cell inflammation, oxidative stress and apoptosis. The present findings suggested that FOXA1 may serve as a target for the treatment of PD.
摘要：
叉头盒A1（FOXA1）在中枢神经系统中起着重要作用，它的丢失会导致酪氨酸羟化酶的下调，直接影响多巴胺的合成，从而导致帕金森病（PD）。本研究旨在探讨FOXA1在PD中的具体作用。收集来自PD患者的血液样品以使用逆转录定量PCR(RT-qPCR)确定FOXA1的表达水平。此外,用6-羟基多巴胺（6-OHDA）诱导小鼠多巴胺能神经元MES23.5细胞构建体外PD模型，以研究FOXA1过表达对细胞炎症的影响，氧化应激和细胞凋亡的RT-qPCR，测定试剂盒和TUNEL测定，分别。随后，沉默FOXA1的表达以评估对下游机制的影响.结果显示，在PD患者中FOXA1的表达水平下调，和FOXA1过表达减弱6-OHDA诱导的炎症，MES23.5细胞的氧化应激和凋亡。此外，FOXA1可以与三叶因子1（TFF1）启动子结合，TFF1沉默逆转了FOXA1过表达对细胞的影响，提示TFF1介导FOXA1在MES23.5细胞中过表达的机制。总之,在FOXA1转录之后，TFF1表达被激活，从而缓解6-OHDA诱导的细胞炎症，氧化应激和细胞凋亡。目前的研究结果表明，FOXA1可以作为治疗PD的靶点。
