Exosomes from TGF-β1-pretreated mesenchymal stem cells alleviate neuronal injury in epilepsy by regulating the miR-132/SIRT1 axis via lncRNA UCA1

Recently, mesenchymal stem cells (MSCs), valued for their multipotent properties, have attracted significant attention in disease therapy. Transforming growth factor-β1(TGF-β1), a cytokine involved in regulating cellular stress responses, is closely associated with neurological function and the differentiation of MSCs. The primary purpose of this research was to assess the neuroprotective capacity of exosomes from TGF-β1-pretreated human umbilical cord mesenchymal stem cells (hUCMSCs) on neuronal injury in epilepsy. In this study, we established epileptic models using male C57BL/6 mice and hippocampal Neurons. Exosomes from TGF-β1- pretreated hUCMSCs were characterized via transmission electron microscopy (TEM) combined with nanoparticle tracking analysis (NTA) and were then applied as a therapeutic intervention. Our research demonstrated that TGF-β1 upregulated the level of the long non-coding RNA urothelial carcinoma-associated 1 (lncRNA UCA1) in hUCMSC-derived exosomes. Exosomes from TGF-β1-pretreated hUCMSCs enhanced neuronal viability, inhibited apoptosis, and reduced inflammation and oxidative stress levels, whereas UCA1 knockdown reversed these beneficial effects. Furthermore, lncRNA UCA1 directly binds to miR-132. Knockdown of UCA1 upregulated miR-132 levels and downregulated SIRT1 expression; this downregulation could be rescued by inhibiting miR-132. In vivo, we further observed that exosomes from TGF-β1-pretreated hUCMSCs alleviated neuronal damage in the hippocampal CA3 region, inhibited glial activation, and suppressed the increase of related inflammatory factors. In contrast, UCA1 knockdown produced the opposite effects. The in vivo findings paralleled the results of the in vitro cell experiments. In conclusion, these results demonstrated that exosomes from TGF-β1-pretreated hUCMSCs exert anti-epileptic effects by modulating the lncRNA UCA1 / miR-132 / SIRT1 axis.