Tan Yong, Zhang Li-Ye, Sun Yue, Luo Xiao-Jie, Wu Si-Yuan, Wu Xian-Zhi, Zhang Yan-Qiong, Wang Ying, Li Bo-Tao, Ni Yi-Ran, Ma Lan, Wu Jiang-Feng
Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, China.
College of Basic Medical Science, China Three Gorges University, Yichang, China.
Mol Ther Nucleic Acids. 2025 Jun 16;36(3):102607. doi: 10.1016/j.omtn.2025.102607. eCollection 2025 Sep 9.
Targeted therapeutics for liver fibrosis (LF) are unavailable. PU.1 is a pioneer transcription factor (TF) that promotes hepatic stellate cell (HSC) activation and LF. PU.1 decoy oligodeoxynucleotides (ODNs) can potentially repress LF by capturing PU.1. In this study, we used Apt-Tan, a hepatic stellate cell (HSC)-internalizing DNA aptamer selected through the cell systematic evolution of ligands by exponential enrichment (Cell-SELEX), and validated the anti-LF effect of a combination of Apt-Tan and PU.1 decoy ODN in mice. Furthermore, intravenous injection of Apt-Tan- PU.1 decoy ODN repressed the expression of PU.1 downstream pro-fibrotic genes such as , alleviated liver injury, and reduced extracellular matrix deposition in mice model of LF induced by CCL. Apt-Tan- PU.1 decoy ODN demonstrated anti-fibrosis potential and warranted further investigation.
目前尚无针对肝纤维化（LF）的靶向治疗药物。PU.1是一种先驱转录因子（TF），可促进肝星状细胞（HSC）激活及肝纤维化。PU.1诱饵寡脱氧核苷酸（ODN）可能通过捕获PU.1来抑制肝纤维化。在本研究中，我们使用了Apt-Tan，一种通过指数富集的配体细胞系统进化（Cell-SELEX）筛选出的可被肝星状细胞（HSC）内化的DNA适配体，并在小鼠中验证了Apt-Tan与PU.1诱饵ODN联合使用的抗肝纤维化作用。此外，静脉注射Apt-Tan-PU.1诱饵ODN可抑制PU.1下游促纤维化基因如[此处原文缺失具体基因名称]的表达，减轻肝损伤，并减少由四氯化碳（CCl）诱导的肝纤维化小鼠模型中的细胞外基质沉积。Apt-Tan-PU.1诱饵ODN显示出抗纤维化潜力，值得进一步研究。
