2. Academic Validation
  3. Schwann cell-secreted frizzled-related protein 1 dictates neuroinflammation and peripheral nerve degeneration after neurotrauma

Schwann cell-secreted frizzled-related protein 1 dictates neuroinflammation and peripheral nerve degeneration after neurotrauma

  • Cell Rep Med. 2024 Oct 14:101791. doi: 10.1016/j.xcrm.2024.101791.
Xiangyun Yao 1,  Lingchi Kong 1,  Yi Qiao 2,  David Brand 3,  Juehong Li 1,  Zhiwen Yan 1,  Song Guo Zheng 4,  Yun Qian 5,  Cunyi Fan 6
Affiliations

Affiliations

  • 1 Department of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China; Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration, Shanghai 200233, China.
  • 2 Department of Sports Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China.
  • 3 The Lt. Col. Luke Weathers, Jr. VA Medical Center, Memphis, TN 38163, USA.
  • 4 Department of Immunology, School of Cell and Gene Therapy, Songjiang Research Institute, Shanghai Songjiang Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 201699, China. Electronic address: song.zheng@shsmu.edu.cn.
  • 5 Department of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China; Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration, Shanghai 200233, China. Electronic address: sakio@sjtu.edu.cn.
  • 6 Department of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China; Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration, Shanghai 200233, China. Electronic address: cyfan@sjtu.edu.cn.
PMID: 39426375 DOI: 10.1016/j.xcrm.2024.101791
Abstract

Neurotrauma in limbs can induce sustained neuroinflammation, resulting in persistent disruption of nerve tissue architecture and retardation of axon regrowth. Despite macrophage-mediated inflammation promoting the removal of necrotic neural components and stimulating neo-vessel ingrowth, detrimental shifts in macrophage phenotype exacerbate nerve degeneration. Herein, we find that peripheral nerve injuries (PNIs) result in abundant secreted frizzled-related protein 1 (sFRP1) expression, particularly by Schwann cells (SCs). Heat shock protein 90 (HSP90) in macrophages recognizes sFRP1 and triggers a dysregulated secretion of inflammatory mediators. Single-cell atlas of human injured peripheral nerves reveals the appearance of sFRP1-expressing SCs with mesenchymal traits and macrophages with a proinflammatory genetic profile. Deletion of either SC-specific sFRP1 or macrophage-specific HSP90 alleviates neuroinflammation and prevents the progression of nerve degeneration. Together, our findings implicate the response of macrophages to SC-derived sFRP1 in exacerbating nerve damage following PNIs.

Keywords

axon regeneration; heat shock protein 90; neuroinflammation; peripheral nerve injury; secreted frizzled-related protein 1.

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  • HY-10858
    99.24%, sFRP-1抑制剂
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