2. Academic Validation
  3. Annexin-A1 SUMOylation regulates microglial polarization after cerebral ischemia by modulating IKKα stability via selective autophagy

Annexin-A1 SUMOylation regulates microglial polarization after cerebral ischemia by modulating IKKα stability via selective autophagy

  • Sci Adv. 2021 Jan 20;7(4):eabc5539. doi: 10.1126/sciadv.abc5539.
Xing Li 1 2 3,  Qian Xia 4,  Meng Mao 1 2 3,  Huijuan Zhou 1 2 3,  Lu Zheng 1 2 3,  Yi Wang 1 2 3,  Zhen Zeng 1 2 3,  Lulu Yan 1 2 3,  Yin Zhao 5,  Jing Shi 6 2 3
Affiliations

Affiliations

  • 1 Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China.
  • 2 Key Laboratory of Neurological Diseases, Ministry of Education, Wuhan 430030, Hubei Province, China.
  • 3 The Institute for Brain Research, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China.
  • 4 Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China.
  • 5 Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China.
  • 6 Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China. sj@mails.tjmu.edu.cn.
PMID: 33523920 DOI: 10.1126/sciadv.abc5539
Abstract

Annexin-A1 (ANXA1) has recently been proposed to play a role in microglial activation after brain ischemia, but the underlying mechanism remains poorly understood. Here, we demonstrated that ANXA1 is modified by SUMOylation, and SUMOylated ANXA1 could promote the beneficial phenotype polarization of microglia. Mechanistically, SUMOylated ANXA1 suppressed nuclear factor κB activation and the production of proinflammatory mediators. Further study revealed that SUMOylated ANXA1 targeted the IκB kinase (IKK) complex and selectively enhanced IKKα degradation. Simultaneously, we detected that SUMOylated ANXA1 facilitated the interaction between IKKα and NBR1 to promote IKKα degradation through selective Autophagy. Further work revealed that the overexpression of SUMOylated ANXA1 in microglia/macrophages resulted in marked improvement in neurological function in a mouse model of cerebral ischemia. Collectively, our study demonstrates a previously unidentified mechanism whereby SUMOylated ANXA1 regulates microglial polarization and strongly indicates that up-regulation of ANXA1 SUMOylation in microglia may provide therapeutic benefits for cerebral ischemia.

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