SP1 transcriptionally activates HTR2B to aggravate traumatic spinal cord injury by shifting microglial M1/M2 polarization

Journal of Orthopaedic Surgery and Research, 2024 · DOI: https://doi.org/10.1186/s13018-024-04678-z · Published: March 14, 2024

Spinal Cord Injury Immunology Genetics

Simple Explanation

Spinal cord injury (SCI) can result in structural and functional damage to the spinal cord, which may lead to loss of limb movement and sensation, loss of bowel and bladder control, and other complications. Macrophages are specialized immune cells that play a critical role in the immune response in various diseases such as musculoskeletal ailments, renal diseases and SCI. The study found that SP1 transcriptionally activated HTR2B to aggravate traumatic SCI by shifting microglial M1/M2 polarization.

Study Duration

Not specified

Participants

Male adult mice, weighting 20–25 g

Evidence Level

Not specified

Key Findings

1
LPS treatment induced cell apoptosis and inhibited microglia polarization from M1 to M2 phenotype, accompanied by an increase of Bax protein expression and a decrease of Bcl-2 protein expression, however, these effects were relieved after SP1 silencing.
2
SP1 transcriptionally activated HTR2B in BV2 cells, and HTR2B knockdown rescued LPS-induced effects on BV2 cell apoptosis and microglial M1/M2 polarization.
3
SCI mouse model assay further showed that SP1 downregulation could attenuate spinal hitting-induced promoting effects on cell apoptosis of spinal cord tissues and microglial M1 polarization.

Research Summary

The study first analyzed the effects of SP1 silencing on biological behaviors of LPS-induced BV2 cells, including cell viability, cell apoptosis, and BV2 microglia polarization. The study continued to analyze the downstream target of SP1 in BV2 cells. We found that SP1 potentially bound to the promoter region of the HTR2B gene, as predicted through the JASPAR online database To reveal the regulatory role of SP1 silencing in microglia polarization in vivo, we established a SCI mouse model.

Practical Implications

Therapeutic Target Identification

SP1 and HTR2B could be potential therapeutic targets for mitigating the effects of spinal cord injury by modulating microglial polarization.

Modulation of Macrophage Phenotype

Modulating the macrophage phenotype towards an anti-inflammatory and tissue repair-promoting state may hold promise for developing therapeutic strategies to enhance recovery and functional outcomes in spinal cord injury.

Drug Development

Drugs targeting the SP1-HTR2B pathway could be developed to promote M2 polarization and reduce inflammation in SCI patients.

Study Limitations

1
Differences in genomics, proteins, and phenotypes between mouse-derived cells and human cells may lead to the irreproducibility of research results.
2
The mouse model may not fully simulate the pathophysiological process of human SCI due to significant differences in the nervous systems between mice and humans.
3
More accurate and human-relevant methods may help to better understand the microglia polarization and cell apoptosis processes after SCI.

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