Mung bean-derived carbon dots suppress ferroptosis of Schwann cells via the Nrf2/HO-1/GPX4 pathway to promote peripheral nerve repair.

Abstract

Schwann cells (SCs) can potentially transform into the repair-related cell phenotype after injury, which can promote nerve repair. Ferroptosis occurs in the SCs of injured tissues, causing damage to the SCs and exacerbating nerve injury. Targeting ferroptosis in SCs is a promising therapeutic strategy for effective repair; however, research on ferroptosis in the peripheral nervous system remains limited. In this study, we generated and characterized novel distinctive carbon dots, mung bean-derived carbon dots (MB-CDs). Our results demonstrated that MB-CDs have the advantages of low toxicity, good biocompatibility, high stability, the specific effect of ferric ions (Fe³⁺) on fluorescence, and antioxidant activity. We demonstrated that MB-CDs promoted functional recovery after peripheral nerve injury (PNI), preventing gastrocnemius atrophy. Further research indicated that MB-CDs boosted the repair-related phenotypes of SCs. We used lipopolysaccharide (LPS) to induce an inflammatory model of SCs and co-cultured them with MB-CDs. Then, we examined the effects of MB-CDs by dividing the cells into four groups: the control group (CTRL), MB-CD treatment group (CDs-SCs), LPS treatment group (LPS-SCs), and LPS and MB-CD treatment group (LPS-CDs). RNA sequencing of LPS-CDs and LPS-SCs indicated that LPS-CDs significantly upregulated heme oxygenase-1 (HO-1) expression. Furthermore, western blotting and immunofluorescence techniques demonstrated that MB-CDs suppressed the ferroptosis of SCs via the Nrf2/HO-1/GPX4 signaling pathway after PNI. Overall, this study further uncovered the connection between ferroptosis and the repair-related phenotypes of SCs, filling this gap in the existing knowledge; accordingly, they may be promising agents for treating PNI.