Fibroblast growth factor 10 stabilizes microtubule and maintains neuronal survival through Rho A/ROCK signal pathway
10.3760/cma.j.cn115354-20220629-00453
- VernacularTitle:成纤维细胞生长因子10通过Rho A/ROCK信号通路稳定微管并维持神经元生存
- Author:
Yongsheng JIANG
1
;
Xiaoxiao DING
;
Jianjun LIN
Author Information
1. 宁波市象山县第一人民医院医疗健康集团科教管理中心，宁波 315700
- Keywords:
Fibroblast growth factor 10;
Microtubule;
Myelin debris;
RAS homologous gene family member A;
Rho A-associated protein kinase
- From:
Chinese Journal of Neuromedicine
2023;22(2):117-126
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the protective effect of fibroblast growth factor 10 (FGF10) on neuronal injury and its potential molecular mechanism.Methods:Cortical neurons were dissected from brain tissues of newborn SD rats and seeded on Poly-L-Lysine coated plates. These neurons were then divided into control group, myelin group and myelin+FGF10 group; after 4 h of culture, neurons in the myelin group were added with a certain content of myelin solution (final concentration: 10 μg/mL), while neurons in the myelin+FGF10 group were added with myelin and FGF10 solution (final concentration: 4.3 nmol/L). One week after culturing, the neuronal apoptosis was detected by TUNEL and flow cytometry; neuronal survival was evaluated by live/dead assay and CCK-8 assay; expressions of apoptosis-related proteins, microtubule related proteins and RAS homologous gene family member A (Rho A)/Rho a-related protein kinase (ROCK) signaling pathway related proteins were detected by Western blotting and immunofluorescent double-label staining.Results:Compared with the control group, the myelin group had significantly increased neuronal apoptosis rate by TUNEL, early neuronal apoptosis rate by flow cytometry, activated cysteine proteinase-3 (caspase-3) protein expression and neuronal mortality rate by live/dead assay, and significantly decreased Bcl-2/Bax value, neuronal survival rate by CCK-8 method, value of acetylated tubulin/Tyr-tubulin (Ace/Tyr-tubulin), Tau protein expression and Ace/Tyr-tubulin fluorescent intensity ratio, and statistically increased Rho A and ROCK protein expressions and Rho A fluorescent intensity ( P<0.05). Compared with the myelin group, the myelin+FGF10 group had significantly decreased neuronal apoptosis rate by TUNEL, early neuronal apoptosis rate by flow cytometry and activated caspase-3 protein expression, significantly increased Bcl-2/Bax value, neuronal survival rate by CCK-8 method, Ace/Tyr-tubulin value, Tau protein expression and Ace/Tyr-tubulin fluorescent intensity ratio, and statistically decreased Rho A and ROCK protein expressions and Rho A fluorescent intensity ( P<0.05). Conclusion:FGF10 maintains microtubule stability in neurons likely through inhibiting Rho A/ROCK axis to antagonize myelin-induced apoptosis and improve the neuronal survival.
