Hepatic-stellate-cell-targeted delivery of PU.1 decoy ODN by Apt-Tan attenuates liver fibrosis in mice.

ABSTRACT: 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 TIMP1, alleviated liver injury, and reduced extracellular matrix deposition in mice model of LF induced by CCL₄. Apt-Tan

SUBMITTER: Tan Y 

PROVIDER: S-EPMC12268346 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature