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糖蛋白非转移性黑色素瘤B与表皮生长因子受体相互作用以调节神经干细胞的存活和分化。

Glycoprotein non-metastatic melanoma B interacts with epidermal growth factor receptor to regulate neural stem cell survival and differentiation.

作者信息

Yang Hua, Jin Gang, Chen Shihong, Luo Jing, Xu Wei

机构信息

Department of Rehabilitation, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China.

Orthopedics Department, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai City, Taizhou, Zhejiang Province, 317000, China.

出版信息

Open Med (Wars). 2023 Feb 14;18(1):20230639. doi: 10.1515/med-2023-0639. eCollection 2023.

Abstract

The functional recovery following spinal cord injury (SCI) remains a challenge clinically. Among the proteins interacted with the , during activation is able to promote the proliferation of neural stem cells (NSCs) in the spinal cord. We investigated the roles of and in regulating the survival and differentiation of the NSCs. By overexpression and short-hairpin RNA-mediated knockdown of in the NSCs, promoted cell viability and differentiation by increasing the expressions of βIII tubulin and CNPase (2',3'-cyclic nucleotide 3-phosphodiesterase). Using co-immunoprecipitation, we found that interacted with . Furthermore, had a similar effect as on promoting cell viability and differentiation. Overexpression of reversed the decrease in viability and differentiation caused by the knockdown of , and . Last but not least, we tested the effect of GPNMB and EGFR on several intracellular pathways and found that modulated the phosphorylated (p)-c-Jun N-terminal kinase (JNK)1/2/JNK1/2 ratio and the p-nuclear factor κB (NF-κB p65)/NF-κB p65 ratio. In sum, our findings demonstrate the interaction between and that regulates cell bioprocesses, with the hope to provide a new strategy of SCI therapy.

摘要

脊髓损伤(SCI)后的功能恢复在临床上仍然是一项挑战。在与……相互作用的蛋白质中,……在激活过程中能够促进脊髓中神经干细胞(NSCs)的增殖。我们研究了……和……在调节神经干细胞存活和分化中的作用。通过在神经干细胞中过表达和短发夹RNA介导的……敲低,……通过增加βIII微管蛋白和2',3'-环核苷酸3-磷酸二酯酶(CNPase)的表达来促进细胞活力和分化。使用免疫共沉淀法,我们发现……与……相互作用。此外,……在促进细胞活力和分化方面与……具有相似的作用。……的过表达逆转了由……和……敲低所导致的活力和分化的降低。最后但同样重要的是,我们测试了糖蛋白非转移性黑色素瘤蛋白B(GPNMB)和表皮生长因子受体(EGFR)对几种细胞内信号通路的影响,发现……调节磷酸化(p)-c-Jun氨基末端激酶(JNK)1/2/JNK1/2的比例以及p-核因子κB(NF-κB p65)/NF-κB p65的比例。总之,我们的研究结果证明了……和……之间的相互作用调节细胞生物过程,希望能为脊髓损伤治疗提供一种新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab4c/9938639/3245acee3c5a/j_med-2023-0639-fig001.jpg

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