Network Analysis Reveals TNF as a Major Hub of Reactive Inflammation Following Spinal Cord Injury

Scientific Reports, 2019 · DOI: 10.1038/s41598-018-37357-1 · Published: January 17, 2019

Spinal Cord Injury Genetics Bioinformatics

Simple Explanation

Spinal cord injury (SCI) leads to reactive inflammation and other harmful events that limit spinal cord regeneration. We treated inflammatory mediators as toxic chemicals and retrieved the genes and interacting proteins associated with them via a set of biological medical databases and software. For achieving a better curative effect on SCI, TNF and other major hubs should be targeted together according to the theory of network intervention, rather than a single target such as TNF alone.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Not specified

Key Findings

1
Tumor necrosis factor (TNF) had the highest scores, and the top 30 were adopted as core data.
2
The core members were involved in cellular responses and metabolic processes, as components of the extracellular space and regions, in protein-binding and receptor-binding functions, as well as in the TNF signaling pathway.
3
Both seizures and SCI were highly associated with TNF levels

Research Summary

We considered SCI-induced inflammatory mediators as a type of toxin that inhibits the regeneration of injured tissue/cells, and we identified the associated genes and interacting proteins from known biological medical databases, CTD26, STRING23, and others According to this study, more than 10,000 genes associated with SCI and TNF achieved the highest score. Notably, the TNF signaling pathways were promoted to the highest enriched level of GAS30 members and had the most significant p-value

Practical Implications

Target Multiple Hubs

Rather than targeting TNF alone, simultaneously targeting other major hubs like FOS and IL6 may yield better therapeutic outcomes.

Repurpose Epilepsy Drugs

Certain drugs used to treat epilepsy could potentially be repurposed as adjuvants in SCI treatment, given the association between seizures and TNF.

Further TNF Studies

TNF could be further connected to aforementioned findings and would be a direction for future SCI studies.

Study Limitations

1
The method hardly describes the dynamic effects of GAS on SCI.
2
Suppressing TNF overexpression might not be a desirable intervention for SCI therapy
3
The primary data mostly overlap with each other.

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