Department of Histology and Embryology, Medical School, Nantong University, Nantong, China.
Wuxi Medical School, Jiangnan University, Wuxi, China.
CNS Neurosci Ther. 2021 Jun;27(6):714-724. doi: 10.1111/cns.13641. Epub 2021 Apr 1.
At the beginning of spinal cord injury (SCI), the expression of EphB2 on fibroblasts and ephrin-B2 on astrocytes increased simultaneously and their binding triggers the formation of astroglial-fibrotic scars, which represent a barrier to axonal regeneration. In the present study, we sought to suppress scar formation and to promote recovery from SCI by targeting EphB2 in vivo.
The female rats SCI models were used in vivo experiments by subsequently injecting with EphB2 shRNA lentiviruses. The effect on EphB2 knockdown was evaluated at 14 days after injury. The repair outcomes were evaluated at 3 months by electrophysiological and morphological assessments to regenerated nerve tissue. The EphB2 expression and TGF-β1 secretion were detected in vitro using a lipopolysaccharides (LPS)-induced astrocyte injury model.
RNAi decreased the expression of EphB2 after SCI, which effectively inhibited fibroblasts and astrocytes from aggregating at 14 days. The expression of EphB2 in activated astrocytes, in addition to fibroblasts, was significantly increased after SCI in vivo, in line with upregulated expression of EphB2 and increased secretion of TGF-β1 in astrocyte culture treated with LPS. Compared to the scramble control, RNAi targeting with EphB2 could promote more nerve regeneration and better myelination.
EphB2 knockdown may effectively inhibit the formation of astroglial-fibrotic scars at the beginning of SCI. It is beneficial to eliminate the barrier of nerve regeneration.
在脊髓损伤（SCI）发生的早期，成纤维细胞上 EphB2 的表达和星形胶质细胞上 ephrin-B2 的表达同时增加，它们的结合触发了星形胶质纤维瘢痕的形成，这是轴突再生的障碍。在本研究中，我们试图通过体内靶向 EphB2 来抑制瘢痕形成并促进 SCI 的恢复。
通过随后注射 EphB2 shRNA 慢病毒，在体内实验中使用雌性大鼠 SCI 模型。在损伤后 14 天评估 EphB2 敲低的效果。通过电生理和形态学评估再生神经组织，在 3 个月时评估修复结果。使用脂多糖（LPS）诱导的星形胶质细胞损伤模型在体外检测 EphB2 的表达和 TGF-β1 的分泌。
RNAi 降低了 SCI 后 EphB2 的表达，有效地抑制了 14 天时成纤维细胞和星形胶质细胞的聚集。EphB2 在激活的星形胶质细胞中的表达，除了成纤维细胞外，在体内 SCI 后也明显增加，与 LPS 处理的星形胶质细胞培养物中 EphB2 的上调表达和 TGF-β1 的增加分泌一致。与 scramble 对照相比，EphB2 的 RNAi 靶向治疗可促进更多的神经再生和更好的髓鞘形成。
EphB2 敲低可有效抑制 SCI 早期星形胶质纤维瘢痕的形成，有利于消除神经再生的障碍。
