Ninj2 regulates Schwann cells development by interfering laminin-integrin signaling

被引:6
|
作者
Sun, Yuxia [1 ]
Chen, Xiang [1 ]
Yue, Cen [2 ,3 ]
Yang, Wenyi [1 ]
Zhang, Shu [1 ]
Ou, Zhimin [4 ]
Chen, Ying [1 ]
机构
[1] Xiamen Univ, Sch Life Sci, State Key Lab Cellular Stress Biol, Xiamen 361005, Fujian, Peoples R China
[2] Xiamen Univ, Affiliated Hosp 1, Sch Med, Dept Neurol, Xiamen, Peoples R China
[3] Brain Ctr, Fujian Key Lab Brain Tumors Diag & Precis Treatmen, Xiamen Key Lab, Xiamen, Peoples R China
[4] Xiamen Univ, Women & Childrens Hosp, Sch Med, Xiamen, Peoples R China
来源
THERANOSTICS | 2022年 / 12卷 / 17期
基金
中国国家自然科学基金;
关键词
Ninj2; Peripheral Nervous System; Myelin; Schwann cell; ITGB1; MYELINATION; DYSTROGLYCAN; GENE; DISRUPTION; MECHANISMS; ADHESION; STROKE; FAK;
D O I
10.7150/thno.76131
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Rationale: Myelin sheath is an important structure to maintain normal functions of the nerves. Nerve Injury-Induced Protein 2 (Ninj2) was found upregulated in Schwann cells (SC) upon injury. However, whether and how Ninj2 plays a role in myelination remain unknown.Methods: In this study, we use transmission electron microscope imaging, immunofluorescent imaging, and behavioral tests to show the effects of Ninj2 on myelination and remyelination in peripheral nervous system (PNS) of SC-specific Ninj2 knockout mice (Dhhcre/+;Ninj2fl/fl). For mechanism studies, we use RNA-Seq analysis to show the Ninj2-related pathways, and co-immunoprecipitation/mass-spectrometry to identify the Ninj2-interacting proteins in SCs. Furthermore, we evaluate the effect of integrin inhibitor GRGDSP during remyelination.Results: Ninj2 negatively regulates SC development. Ninj2-deficient mice exhibit precocious myelination phenotype, as well as the accelerated remyelination process after sciatic nerve injury. Loss of Ninj2 promotes myelination by promoting SC proliferation to augment its population. Mechanistically, Ninj2 interacted with ITGB1 on SC membrane, which inhibits laminin-integrin signaling. Removal of Ninj2 induces the activity of laminin-integrin signaling, resulting in the improved myelination in the Dhhcre/+;Ninj2fl/fl mice. Inhibition of laminin-integrin signaling by integrin inhibitor GRGDSP sufficiently delays the remyelination process in the Dhhcre/+;Ninj2fl/fl mice with sciatic nerve injury.Conclusion: Our study found Ninj2 as a negative regulator in the network controlling myelination in the PNS.
引用
收藏
页码:7307 / 7318
页数:12
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