Department of Neurosurgery Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders, Chongqing 400010, China.
Center for Neuroscience Research, Chongqing Medical University, Chongqing 400016, China.
Int J Mol Sci. 2024 Jan 24;25(3):1438. doi: 10.3390/ijms25031438.
Transcription factors within microglia contribute to the inflammatory response following intracerebral hemorrhage (ICH). Therefore, we employed bioinformatics screening to identify the potential transcription factor tonicity-responsive enhancer-binding protein (TonEBP) within microglia. Inflammatory stimuli can provoke an elevated expression of TonEBP in microglia. Nevertheless, the expression and function of microglial TonEBP in ICH-induced neuroinflammation remain ambiguous. In our recent research, we discovered that ICH instigated an increased TonEBP in microglia in both human and mouse peri-hematoma brain tissues. Furthermore, our results indicated that TonEBP knockdown mitigates lipopolysaccharide (LPS)-induced inflammation and the activation of NF-κB signaling in microglia. In order to more deeply comprehend the underlying molecular mechanisms of how TonEBP modulates the inflammatory response, we sequenced the transcriptomes of TonEBP-deficient cells and sought potential downstream target genes of TonEBP, such as Pellino-1 (PELI1). PELI has been previously reported to mediate nuclear factor-κB (NF-κB) signaling. Through the utilization of CUT & RUN, a dual-luciferase reporter, and qPCR, we confirmed that TonEBP is the transcription factor of , binding to the promoter. In summary, TonEBP may enhance the LPS-induced inflammation and activation of NF-κB signaling via PELI1.
转录因子在脑血肿（ICH）后炎症反应中起作用。因此，我们采用生物信息学筛选来鉴定小胶质细胞中潜在的转录因子渗透压反应增强结合蛋白（TonEBP）。炎症刺激可以引发小胶质细胞中 TonEBP 的表达升高。然而，小胶质细胞 TonEBP 在 ICH 诱导的神经炎症中的表达和功能仍不清楚。在我们最近的研究中，我们发现ICH 在人及鼠血肿周围脑组织中的小胶质细胞中引发 TonEBP 增加。此外，我们的结果表明 TonEBP 敲低可减轻脂多糖（LPS）诱导的小胶质细胞炎症和 NF-κB 信号通路的激活。为了更深入地了解 TonEBP 调节炎症反应的潜在分子机制，我们对 TonEBP 缺陷细胞的转录组进行了测序，并寻找 TonEBP 的潜在下游靶基因，如 Pellino-1（PELI1）。PELI 先前被报道介导核因子-κB（NF-κB）信号通路。通过使用 CUT & RUN、双荧光素酶报告基因和 qPCR，我们证实 TonEBP 是结合到 启动子的转录因子。总之，TonEBP 可能通过 PELI1 增强 LPS 诱导的炎症和 NF-κB 信号通路的激活。
