| First Author | Li X | Year | 2021 |
| Journal | Sci Adv | Volume | 7 |
| Issue | 4 | PubMed ID | 33523920 |
| Mgi Jnum | J:308633 | Mgi Id | MGI:6728236 |
| Doi | 10.1126/sciadv.abc5539 | Citation | Li X, et al. (2021) Annexin-A1 SUMOylation regulates microglial polarization after cerebral ischemia by modulating IKKalpha stability via selective autophagy. Sci Adv 7(4) |
| abstractText | 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 kappaB activation and the production of proinflammatory mediators. Further study revealed that SUMOylated ANXA1 targeted the IkappaB kinase (IKK) complex and selectively enhanced IKKalpha degradation. Simultaneously, we detected that SUMOylated ANXA1 facilitated the interaction between IKKalpha and NBR1 to promote IKKalpha 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. |
