| First Author | Liu J | Year | 2022 |
| Journal | iScience | Volume | 25 |
| Issue | 12 | Pages | 105527 |
| PubMed ID | 36465125 | Mgi Jnum | J:332006 |
| Mgi Id | MGI:7407787 | Doi | 10.1016/j.isci.2022.105527 |
| Citation | Liu J, et al. (2022) Inhibition of the LRRC8A channel promotes microglia/macrophage phagocytosis and improves outcomes after intracerebral hemorrhagic stroke. iScience 25(12):105527 |
| abstractText | Promoting microglial/macrophage (M/Mphi) phagocytosis accelerates hematoma clearance and improves the prognosis of intracerebral hemorrhagic stroke (ICH). Cation channels such as Piezo1 modulate bacterial clearance by regulating M/Mphi. Whether LRRC8A, an anion channel, affects M/Mphi erythrophagocytosis and functional recovery after ICH was investigated here. We found that LRRC8A is highly expressed on M/Mphi in the perihematomal region of ICH mice. Conditional knockout of Lrrc8a in M/Mphi or treatment with an LRRC8A channel blocker accelerated hematoma clearance, reduced neuronal death, and improved functional recovery after ICH. Mechanistically, the LRRC8A channel inhibition promoted M/Mphi phagocytosis by activating AMP-activated protein kinase (AMPK), thereby inducing nuclear translocation of nuclear factor-erythroid 2 related factor 2 (Nrf2) and increasing Cd36 transcription. Our findings illuminate the regulation of M/Mphi phagocytosis by the LRRC8A channel via the AMPK-Nrf2-CD36 pathway after ICH, suggesting that LRRC8A is a potential target for hematoma clearance in ICH treatment. |
