BAP1 controls mesenchymal stem cell migration by inhibiting the ERK signaling pathway.

IF 2.9 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY BMB Reports Pub Date : 2024-05-01

Seobin Kim, Eun-Woo Lee, Doo-Byoung Oh, Jinho Seo

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Abstract

Due to their stem-like characteristics and immunosuppressive properties, Mesenchymal stem cells (MSCs) offer remarkable potential in regenerative medicine. Much effort has been devoted to enhancing the efficacy of MSC therapy by enhancing MSC migration. In this study, we identified deubiquitinase BRCA1- associated protein 1 (BAP1) as an inhibitor of MSC migration. Using deubiquitinase siRNA library screening based on an in vitro wound healing assay, we found that silencing BAP1 significantly augmented MSC migration. Conversely, BAP1 overexpression reduced the migration and invasion capabilities of MSCs. BAP1 depletion in MSCs upregulates ERK phosphorylation, thereby increasing the expression of the migration factor, osteopontin. Further examination revealed that BAP1 interacts with phosphorylated ERK1/2, deubiquitinating their ubiquitins, and thus attenuating the ERK signaling pathway. Overall, our study highlights the critical role of BAP1 in regulating MSC migration through its deubiquitinase activity, and suggests a novel approach to improve the therapeutic potential of MSCs in regenerative medicine. [BMB Reports 2024; 57(5): 250-255].

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BAP1通过抑制ERK信号通路控制间充质干细胞迁移。

间充质干细胞(MSCs)由于其干细胞样特性和免疫抑制特性在再生医学中具有显著的潜力。通过促进骨髓间充质干细胞迁移来提高骨髓间充质干细胞治疗的疗效已经付出了很多努力。在这项研究中，我们发现去泛素酶brca1相关蛋白1 (BAP1)是MSC迁移的抑制剂。基于体外伤口愈合实验，使用去泛素酶siRNA文库筛选，我们发现沉默BAP1可显著增强MSC迁移。相反，BAP1过表达降低了MSCs的迁移和侵袭能力。MSCs中BAP1缺失上调ERK磷酸化，从而增加迁移因子骨桥蛋白的表达。进一步研究发现，BAP1与磷酸化的ERK1/2相互作用，使其泛素化，从而减弱ERK信号通路。总的来说，我们的研究强调了BAP1通过其去泛素酶活性在调节MSC迁移中的关键作用，并提出了一种新的方法来提高MSC在再生医学中的治疗潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

BMB Reports 生物-生化与分子生物学

CiteScore

5.10

自引率

7.90%

发文量

141

审稿时长

1 months

期刊介绍： The BMB Reports (BMB Rep, established in 1968) is published at the end of every month by Korean Society for Biochemistry and Molecular Biology. Copyright is reserved by the Society. The journal publishes short articles and mini reviews. We expect that the BMB Reports will deliver the new scientific findings and knowledge to our readers in fast and timely manner.