TNF‐ α ‐Induced KAT2A Impedes BMMSC Quiescence by Mediating Succinylation of the Mitophagy‐Related Protein VCP

作者：Zepeng Su, Jinteng Li, Jiajie Lin, Zhikun Li, Yunshu Che, Zhaoqiang Zhang, Zheng Guan, Guiwen Ye, Wenhui Yu, Yipeng Zeng, Peitao Xu, Xiaojun Xu, Zhongyu Xie, Yanfeng Wu, Huiyong Shen · 发表于：Advanced Science · 年份：2023 · DOI：10.1002/advs.202303388 · 被引用次数：20 · 研究领域：Mesenchymal stem cell research、Autophagy in Disease and Therapy、Electrospun Nanofibers in Biomedical Applications

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.