Imatinib inhibits pericyte‑fibroblast transition and inflammation and promotes axon regeneration by blocking the PDGF‑BB/PDGFRβ pathway in spinal cord injury

Inflammation and Regeneration, 2022 · DOI: https://doi.org/10.1186/s41232-022-00223-9 · Published: September 2, 2022

Spinal Cord Injury Cardiovascular Science Genetics

Simple Explanation

Spinal cord injuries (SCI) often lead to fibrotic scar formation and inflammation, hindering axon regeneration and causing permanent functional deficits. This study investigates the role of pericytes, which transform into fibroblasts and contribute to fibrotic scar formation after SCI. The study found that microvascular endothelial cells induce pericyte-fibroblast transition through the PDGF-BB/PDGFRβ signaling pathway. Blocking this pathway with imatinib promoted motor function recovery and axonal regeneration, while inhibiting fibrotic scar formation. The researchers discovered that imatinib, a selective PDGFRβ inhibitor, reduced microvessel leakage and inflammation, contributing to functional recovery after SCI. These findings suggest a potential therapeutic target for SCI treatment.

Study Duration

28 days

Participants

C57BL/6J female mice

Evidence Level

Not specified

Key Findings

1
PDGFRβ+ pericytes detach from blood vessel walls and transition into fibroblasts to form fibrotic scar after SCI, indicating a key role in scar formation.
2
Microvascular endothelial cells, as a source of PDGF-BB, induce pericyte-fibroblast transition via the PDGF-BB/PDGFRβ signaling pathway, highlighting a mechanism for scar formation.
3
Pharmacologically blocking the PDGF-BB/PDGFRβ pathway with imatinib promotes motor function recovery, axonal regeneration, and inhibits fibrotic scar formation after SCI, suggesting a therapeutic strategy.

Research Summary

This study investigates the mechanism of pericyte-fibroblast transition after spinal cord injury (SCI) and the role of the PDGF-BB/PDGFRβ signaling pathway in this process. The results show that microvascular endothelial cells induce pericyte-fibroblast transition through the PDGF-BB/PDGFRβ signaling pathway, contributing to fibrotic scar formation after SCI. Pharmacological inhibition of the PDGF-BB/PDGFRβ signaling pathway with imatinib promotes functional recovery, axonal regeneration, and reduces fibrotic scarring and inflammation after SCI, suggesting a potential therapeutic target.

Practical Implications

Therapeutic Target

Blocking the PDGF-BB/PDGFRβ signaling pathway may provide a therapeutic strategy for spinal cord injury by reducing fibrotic scarring and promoting axonal regeneration.

Drug Development

Imatinib or similar PDGFRβ inhibitors could be further developed for clinical use in SCI patients to improve functional outcomes.

Cellular Crosstalk

Understanding the crosstalk between microvascular endothelial cells and pericytes may lead to novel approaches for modulating the microenvironment after SCI.

Study Limitations

1
The study focuses on female mice, and results may not be generalizable to males.
2
The study uses a crush SCI model, which may not fully replicate the complexities of human SCI.
3
The long-term effects of imatinib treatment on spinal cord tissue and function were not fully evaluated.

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