Zheng Fei, Zhang Yumin, Zhou Hui, Li Jiangnan, Gao Junyang, Qu Xiaoli, Wu Xuejian, Lu Siyu, Wang Yuanyi, Zhou Nan
Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou 450052, China.
Department of Geriatric Endocrinology, The First Hospital Affiliated to Nanjing Medical University, Nanjing 210029, China.
Biomater Sci. 2025 May 13;13(10):2656-2672. doi: 10.1039/d4bm01570c.
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 (Fe) 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 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.
雪旺细胞（SCs）在损伤后有可能转变为与修复相关的细胞表型，从而促进神经修复。铁死亡发生在受损组织的雪旺细胞中，对雪旺细胞造成损伤并加重神经损伤。针对雪旺细胞中的铁死亡是一种有前景的有效修复治疗策略；然而，关于周围神经系统中铁死亡的研究仍然有限。在本研究中，我们制备并表征了新型独特的碳点，即绿豆衍生碳点（MB - CDs）。我们的结果表明，MB - CDs具有低毒性、良好的生物相容性、高稳定性、铁离子（Fe）对荧光的特异性作用以及抗氧化活性。我们证明MB - CDs促进周围神经损伤（PNI）后的功能恢复，防止腓肠肌萎缩。进一步的研究表明，MB - CDs增强了雪旺细胞与修复相关的表型。我们使用脂多糖（LPS）诱导雪旺细胞的炎症模型，并将它们与MB - CDs共培养。然后，我们将细胞分为四组来研究MB - CDs的作用：对照组（CTRL）、MB - CD处理组（CDs - SCs）、LPS处理组（LPS - SCs）和LPS与MB - CD处理组（LPS - CDs）。对LPS - CDs和LPS - SCs进行RNA测序表明，LPS - CDs显著上调血红素加氧酶-1（HO - 1）的表达。此外，蛋白质免疫印迹和免疫荧光技术表明，MB - CDs在PNI后通过Nrf2/HO - 1/GPX4信号通路抑制雪旺细胞的铁死亡。总体而言，本研究进一步揭示了铁死亡与雪旺细胞修复相关表型之间的联系，填补了现有知识中的这一空白；因此，它们可能是治疗PNI的有前景的药物。
