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Inhibition of CD44 suppresses the formation of fibrotic scar after spinal cord injury via the JAK2/STAT3 signaling pathway

iScience, 2024 · DOI: https://doi.org/10.1016/j.isci.2024.108935 · Published: February 16, 2024

Spinal Cord InjuryNeurologyPathology

Simple Explanation

This study investigates the role of CD44 in fibrotic scar formation after spinal cord injury (SCI). It found that CD44 expression increases during scar formation. Blocking CD44 with the IM7 antibody reduces the expression of fibrosis-related proteins and promotes axon regeneration across the scar. The study also explores the underlying mechanisms, revealing that CD44 influences fibrotic scar formation via the JAK2/STAT3 signaling pathway in an inflammatory environment.

Study Duration
2 and 12 weeks
Participants
C57 BL/6 female mice aged 8–10 weeks
Evidence Level
Not specified

Key Findings

  • 1
    CD44 is upregulated during the formation of fibrotic scar after spinal cord injury.
  • 2
    Blocking CD44 with IM7 reduces fibrosis-related extracellular matrix protein expression and promotes corticospinal tract axon regeneration across the scar.
  • 3
    CD44 modulates fibrotic scar formation in the inflammatory microenvironment via the JAK2/STAT3 signaling pathway.

Research Summary

The study found that CD44 was upregulated during fibrotic scar formation after SCI. Blocking CD44 downregulated fibrosis-related extracellular matrix proteins and promoted axon regeneration, leading to improved motor and sensory function. In vitro experiments showed that inhibiting CD44 and the JAK2/STAT3 pathway decreased fibroblast proliferation, differentiation, and migration induced by inflammatory supernatant.

Practical Implications

Therapeutic Target Identification

CD44 and its downstream JAK2/STAT3 signaling pathway are potential therapeutic targets for treating fibrotic scar formation after SCI.

Functional Recovery Improvement

Targeting CD44 can promote axon regeneration and improve motor and sensory function recovery after spinal cord injury.

Inflammatory Microenvironment Modulation

Modulating the inflammatory microenvironment by inhibiting CD44 may provide a strategy to reduce fibrotic scar formation and enhance functional recovery.

Study Limitations

  • 1
    JAK2/STAT3 signaling may not be the sole pathway implicated in CD44-mediated fibrosis.
  • 2
    Certain fibrosis-related proteins did not return to the control level in the presence of an inflammatory microenvironment, despite the inhibition of this pathway.
  • 3
    Further investigations are warranted to substantiate whether other concurrent molecular pathways may be involved in this process.

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