Department of Surgery, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
BMC Genomics. 2011 Feb 25;12:128. doi: 10.1186/1471-2164-12-128.
Hepatocyte nuclear factor 4α (HNF4α), a liver-specific transcription factor, plays a significant role in liver-specific functions. However, its functions are poorly understood in the regulation of the inflammatory response. In order to obtain a genomic view of HNF4α in this context, microarray analysis was used to probe the expression profile of an inflammatory response induced by cytokine stimulation in a model of HNF4α knock-down in HepG2 cells.
The expression of over five thousand genes in HepG2 cells is significantly changed with the dramatic reduction of HNF4α concentration compared to the cells with native levels of HNF4α. Over two thirds (71%) of genes that exhibit differential expression in response to cytokine treatment also reveal differential expression in response to HNF4α knock-down. In addition, we found that a number of HNF4α target genes may be indirectly mediated by an ETS-domain transcription factor ELK1, a nuclear target of mitogen-activated protein kinase (MAPK).
The results indicate that HNF4α has an extensive impact on the regulation of a large number of the liver-specific genes. HNF4α may play a role in regulating the cytokine-induced inflammatory response. This study presents a novel function for HNF4α, acting not only as a global player in many cellular processes, but also as one of the components of inflammatory response in the liver.
肝细胞核因子 4α（HNF4α）是一种肝脏特异性转录因子，在肝脏特异性功能中发挥重要作用。然而，其在炎症反应调控中的功能知之甚少。为了从基因组水平上了解 HNF4α在这方面的作用，我们使用微阵列分析方法研究了在 HepG2 细胞中敲低 HNF4α 模型中细胞因子刺激诱导的炎症反应的表达谱。
与具有天然 HNF4α 水平的细胞相比，HepG2 细胞中超过五千个基因的表达在 HNF4α 浓度显著降低的情况下发生了显著变化。超过三分之二（71%）对细胞因子处理有差异表达的基因也对 HNF4α 敲低有差异表达。此外，我们发现许多 HNF4α 靶基因可能是通过细胞外信号调节激酶（MAPK）的核靶标 ETS 结构域转录因子 ELK1 间接介导的。
这些结果表明，HNF4α 对大量肝脏特异性基因的调控有广泛的影响。HNF4α 可能在调节细胞因子诱导的炎症反应中发挥作用。本研究揭示了 HNF4α 的一个新功能，它不仅作为许多细胞过程的全局调控因子，而且作为肝脏炎症反应的组成部分之一。
