Molecular Mechanism of MiR-136-5p Targeting NF-κB/A20 in the IL-17-Mediated Inflammatory Response after Spinal Cord Injury

被引:64
作者
He, Jichen [1 ]
Zhao, Jinmin [3 ,4 ,5 ]
Peng, Xiaoming [1 ]
Shi, Xiongzhi [1 ]
Zong, Shaohui [1 ,4 ,5 ]
Zeng, Gaofeng [2 ,4 ]
机构
[1] Guangxi Med Univ, Dept Spine Osteopathia, Affiliated Hosp 1, Nanning, Guangxi, Peoples R China
[2] Guangxi Med Univ, Coll Publ Hyg, Nanning, Guangxi, Peoples R China
[3] Guangxi Med Univ, Dept Osteopathia, Affiliated Hosp 1, Nanning, Guangxi, Peoples R China
[4] Guangxi Med Univ, Res Ctr Regenerat Med, Nanning, Guangxi, Peoples R China
[5] Guangxi Med Univ, Guangxi Key Lab Regenerat Med, Nanning, Guangxi, Peoples R China
基金
中国国家自然科学基金;
关键词
Rat Astrocyte; MicroRNAs; Viral Transfection; NF-kappa B/A20; Spinal Cord Injury; NF-KAPPA-B; MULTIPLE-SCLEROSIS; IN-VITRO; ASTROCYTES; CELLS; A20; EXPRESSION; KINASE; ALPHA; IL-17;
D O I
10.1159/000485452
中图分类号
Q2 [细胞生物学];
学科分类号
071013 [干细胞生物学];
摘要
Background/Aims: The pathophysiology of spinal cord injury (SCI) results in serious damage to the human body via an increase in the secondary biological processes imposed by activated astrocytes. Abnormal expression of microRNAs after SCI has become a potential research focus. However, the underlying mechanisms are poorly understood. Methods: SCI models were established in rats using Allen's method, and the BBB scoring method was employed to assess locomotor function. Lentivirus was used to infect rat astrocytes and SCI rats. Real-time PCR and antibody chip were used to measure gene expression and cytokine secretion. Western blot analysis was employed to detect protein expression. HE staining was used to assess the histological changes in SCI. The immunohistochemical staining of A20 and p-NF-kappa B in SCI was also analyzed. Results: The in vitro experiment showed that miR-136- 5p up-regulated the expression of p-NF-kappa B by down-regulating the expression of A20 so that astrocytes produced inflammatory factors and chemokines. The in vivo experiment indicated that overexpressed miR-136-5p promoted the production of inflammatory factors, chemokines and p-NF-kappa B in SCI rats, whereas it inhibited the expression of A20 protein and increased inflammatory cell infiltration and injuries in the spinal cord. Conclusion: The current findings indicate that silencing miR-136-5p effectively decreased inflammatory factors and chemokines and protected the spinal cord via NF-kappa B/A20 signaling in vivo and in vitro. In contrast, overexpression of miR-136-5p had the opposite effect. (C) 2017 The Author(s) Published by S. Karger AG, Basel
引用
收藏
页码:1224 / 1241
页数:18
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