CHI3L1 drives astrocyte-medicated neuronal injury via GAL3-NLRP3 signaling in ischemic stroke

  1. Haiyan Li
  2. Ying Deng
  3. Jinan Chen
  4. Yubao Lu
  5. Yinyao Lin
  6. Xuejiao Men
  7. Yuyan Zeng
  8. Haoyang Li
  9. Guangyou Wang
  10. Yu-Wen Alvin Huang
  11. Bingjun Zhang
  12. Ziqi Liang
  13. Da Mi
  14. Xuan Li
  15. Changyong Tang
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Abstract

Background: Ischemic stroke lacks effective therapies. Whether chitinase-3-like protein 1 (CHI3L1) is involved in astrocyte-mediated neuronal injury, and its regulatory mechanism in both patient serum and ischemic brain tissue, remain largely unknown. Methods: We combined clinical proteomics, mouse tMCAO, in vitro OGD models, and genetic/pharmacological interventions to define CHI3L1 expression, function and downstream signaling. Results: CHI3L1 is robustly elevated in stroke patient serum and astrocytes in peri-infarct brain, correlating with stroke severity. CHI3L1 aggravates neuronal apoptosis, BBB disruption and functional deficits by activating GAL3–NLRP3 inflammasome. Astrocyte-specific GAL3 silencing or GB1107 inhibition markedly mitigates ischemic injury. Conclusion: The CHI3L1–GAL3–NLRP3 axis drives astrocyte-mediated neuronal damage in ischemic stroke, representing a promising therapeutic target.

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  1. Version published to 10.21203/rs.3.rs-9462748/v1 on Research Square