Identiﬁcation of canonical pyroptosis-related genes, associated regulation axis, and related traditional Chinese medicine in spinal cord injury

Front. Aging Neurosci., 2023 · DOI: 10.3389/fnagi.2023.1152297 · Published: May 18, 2023

Spinal Cord Injury Neurology Bioinformatics

Simple Explanation

Spinal cord injury (SCI) often leads to irreversible sensory and motor dysfunction, resulting in lifelong disability of patients and a heavy burden on society. Currently, there is no eﬀective cure for SCI. Neuroinﬂammation plays an important role in secondary injury and studying the mechanism of neuroinﬂammation may provide potential therapeutic targets for treating SCI. Pyroptosis is inﬂammatory-related programmed cell death and the gasdermin protein family is the executioner of pyroptosis.

Study Duration

acute, subacute and chronic stages

Participants

rat and mouse SCI models

Evidence Level

Not specified

Key Findings

1
The AIM2/NLRC4/NLRP3 inﬂammasome-related genes, GSDMD, IL1B, and IL18, were highly expressed in SCI.
2
39 up-regulated TFs were identiﬁed, which may regulate at least two of NLRP3/PRGs.
3
A total of 7 down-regulated miRNAs were identiﬁed which could regulate Nlrp3/PRGs.

Research Summary

We downloaded raw counts data of seven high-throughput sequencings and two microarray datasets from the GEO database, classiﬁed by species (rat and mouse) and SCI modes (moderate contusive model, aneurysm clip impact-compression model, and hemisection model), including mRNAs, miRNAs, lncRNAs, and circRNAs, basically covering the acute, subacute and chronic stages of SCI. We performed differential analysis by R (DEseq2) or GEO2R and found that the AIM2/NLRC4/NLRP3 inﬂammasome-related genes, GSDMD, IL1B, and IL18, were highly expressed in SCI. Finally, 39 up-regulated TFs were identiﬁed, which may regulate at least two of NLRP3/PRGs. A total of 7 down-regulated miRNAs were identiﬁed which could regulate Nlrp3/PRGs.

Practical Implications

Therapeutic Targets

The identiﬁed pyroptosis-related genes and their regulatory mechanisms offer potential therapeutic targets for treating spinal cord injury by modulating neuroinﬂammation.

Drug Development

The predicted Traditional Chinese Medicine (TCM) and small drug-like molecules with NLRP3/PRGs as potential targets can be further explored for drug development.

Personalized Medicine

Understanding the differential expression of pyroptosis-related genes in different SCI models can lead to personalized treatment strategies.

Study Limitations

1
Because of the particularity of SCI disease, the human body sample study is fewer, and most of the studies are based on animal models.
2
A single animal model cannot fully reﬂect the pathological process of the disease in the human body.
3
At present, there is a lack of systematic research on SCI pyroptosis and its regulation mechanism.

Your Feedback

Was this summary helpful?

Back to Spinal Cord Injury