周围神经损伤(PNI)通常导致显著的功能损害。这里,我们研究了含表皮生长因子样结构域的蛋白7(EGFL7)对PNI后血管生成和神经再生的影响.使用坐骨神经损伤模型,我们使用坐骨神经功能指数评估神经功能。我们分析了EGFL7,叉头盒蛋白A1(FOXA1)的表达水平,神经生长因子(NGF),脑源性神经营养因子(BDNF),神经丝200(NF200),髓磷脂蛋白零(P0),细胞粘附分子1(CD31),血管内皮生长因子(VEGF),以及组织和细胞中的NOTCH相关蛋白。细胞增殖,迁移,和血管生成通过细胞计数试剂盒测定进行评估,5-乙炔基-2脱氧尿苷染色,和Transwell分析。我们使用双荧光素酶测定和染色质免疫沉淀研究了FOXA1与EGFL7启动子的结合。我们观察到PNI中EGFL7表达减少和FOXA1表达增加,和EGFL7过表达减轻腓肠肌萎缩,增加肌肉重量,和改善运动功能。此外,EGFL7过表达增强雪旺细胞和内皮细胞的增殖和迁移,促进管形成,并上调NGF,BDNF,NF200、P0、CD31和VEGF表达。发现FOXA1与EGFL7启动子区结合,抑制EGFL7表达并激活NOTCH信号通路。值得注意的是,FOXA1过表达抵消了EGFL7对雪旺细胞和内皮细胞的影响。总之,EGFL7有望作为治疗坐骨神经损伤的治疗分子。
Peripheral nerve injury (PNI) often leads to significant functional impairment. Here, we investigated the impact of epidermal growth factor-like domain-containing protein 7 (
EGFL7) on angiogenesis and nerve regeneration following PNI. Using a sciatic nerve injury model, we assessed nerve function using the sciatic nerve function index. We analyzed the expression levels of
EGFL7, forkhead box proteins A1 (FOXA1), nerve growth factor (NGF), brain-derived neurotrophic factors (BDNF), Neurofilament 200 (NF200), myelin protein zero (P0), cell adhesion molecule 1 (CD31), vascular endothelial growth factor (VEGF), and NOTCH-related proteins in tissues and cells. Cell proliferation, migration, and angiogenesis were evaluated through cell counting kit assays, 5-ethynyl-2\'deoxyuridine staining, and Transwell assays. We investigated the binding of FOXA1 to the EGFL7 promoter using dual-luciferase assays and chromatin immunoprecipitation. We observed decreased
EGFL7 expression and increased FOXA1 expression in PNI, and
EGFL7 overexpression alleviated gastrocnemius muscle atrophy, increased muscle weight, and improved motor function. Additionally, EGFL7 overexpression enhanced Schwann cell and endothelial cell proliferation and migration, promoted tube formation, and upregulated NGF, BDNF, NF200, P0, CD31, and VEGF expression. FOXA1 was found to bind to the
EGFL7 promoter region, inhibiting
EGFL7 expression and activating the NOTCH signaling pathway. Notably, FOXA1 overexpression counteracted the effects of EGFL7 on Schwann cells and endothelial cells. In conclusion,
EGFL7 holds promise as a therapeutic molecule for treating sciatic nerve injury.