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TNF-α-Induced KAT2A Impedes BMMSC Quiescence by Mediating Succinylation of the Mitophagy-Related Protein VCP
Advanced Science ( IF 14.3 ) Pub Date : 2023-12-25 , DOI: 10.1002/advs.202303388 Zepeng Su 1 , Jinteng Li 1 , Jiajie Lin 1 , Zhikun Li 1 , Yunshu Che 1 , Zhaoqiang Zhang 1 , Guan Zheng 1 , Guiwen Ye 1 , Wenhui Yu 1 , Yipeng Zeng 1 , Peitao Xu 1 , Xiaojun Xu 1 , Zhongyu Xie 1 , Yanfeng Wu 2 , Huiyong Shen 1
Advanced Science ( IF 14.3 ) Pub Date : 2023-12-25 , DOI: 10.1002/advs.202303388 Zepeng Su 1 , Jinteng Li 1 , Jiajie Lin 1 , Zhikun Li 1 , Yunshu Che 1 , Zhaoqiang Zhang 1 , Guan Zheng 1 , Guiwen Ye 1 , Wenhui Yu 1 , Yipeng Zeng 1 , Peitao Xu 1 , Xiaojun Xu 1 , Zhongyu Xie 1 , Yanfeng Wu 2 , Huiyong Shen 1
Affiliation
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Regular quiescence and activation are important for the function of bone marrow mesenchymal stem cells (BMMSC), multipotent stem cells that are widely used in the clinic due to their capabilities in tissue repair and inflammatory disease treatment. TNF-α is previously reported to regulate BMMSC functions, including multilineage differentiation and immunoregulation. The present study demonstrates that TNF-α impedes quiescence and promotes the activation of BMMSC in vitro and in vivo. Mechanistically, the TNF-α-induced expression of KAT2A promotes the succinylation of VCP at K658, which inhibits the interaction between VCP and MFN1 and thus inhibits mitophagy. Furthermore, activated BMMSC exhibits stronger fracture repair and immunoregulation functions in vivo. This study contributes to a better understanding of the mechanisms of BMMSC quiescence and activation and to improving the effectiveness of BMMSC in clinical applications.
中文翻译：
TNF-α 诱导的 KAT2A 通过介导线粒体自噬相关蛋白 VCP 的琥珀酰化来阻碍 BMMSC 静止
定期的静止和激活对于骨髓间充质干细胞（BMMSC）的功能非常重要，这种多能干细胞因其在组织修复和炎症性疾病治疗方面的能力而广泛应用于临床。此前有报道称 TNF- α可调节 BMMSC 功能，包括多谱系分化和免疫调节。本研究表明，TNF- α可在体外和体内阻碍 BMMSC 的静止并促进其激活。从机制上讲，TNF- α诱导的KAT2A表达促进VCP在K658处的琥珀酰化，从而抑制VCP和MFN1之间的相互作用，从而抑制线粒体自噬。此外，活化的BMMSC在体内表现出更强的骨折修复和免疫调节功能。本研究有助于更好地理解BMMSC静止和激活的机制，并提高BMMSC在临床应用中的有效性。
更新日期：2023-12-25
中文翻译：
TNF-α 诱导的 KAT2A 通过介导线粒体自噬相关蛋白 VCP 的琥珀酰化来阻碍 BMMSC 静止
定期的静止和激活对于骨髓间充质干细胞（BMMSC）的功能非常重要，这种多能干细胞因其在组织修复和炎症性疾病治疗方面的能力而广泛应用于临床。此前有报道称 TNF- α可调节 BMMSC 功能，包括多谱系分化和免疫调节。本研究表明，TNF- α可在体外和体内阻碍 BMMSC 的静止并促进其激活。从机制上讲，TNF- α诱导的KAT2A表达促进VCP在K658处的琥珀酰化，从而抑制VCP和MFN1之间的相互作用，从而抑制线粒体自噬。此外，活化的BMMSC在体内表现出更强的骨折修复和免疫调节功能。本研究有助于更好地理解BMMSC静止和激活的机制，并提高BMMSC在临床应用中的有效性。
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