ArticleFrontiers in genetics2026
Integrative analysis identifies Hspa5 as a key regulator of the ERS/UPR-immune axis in spinal cord injury.
Article in Frontiers in genetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Endoplasmic reticulum stress (ERS) and the unfolded protein response (UPR) are critical in secondary spinal cord injury (SCI), but their systematic characterization and link to immune infiltration remain unclear. This study aimed to identify key ERS/UPR-related genes and their association with the immune microenvironment to find robust biomarkers for SCI. Methods: We analyzed bulk RNA-seq data (GSE151371) to identify differentially expressed genes (DEGs), followed by pathway enrichment analyses. Machine learning (SVM-RFE) and protein-protein interaction networks were used to screen for hub genes. The identified hub genes were validated using an independent cohort (GSE5296), single-cell sequencing data (GSE213240), and qRT-PCR in a murine SCI model. Results: We identified 17 ERS-related and 27 UPR-related DEGs, primarily enriched in neuron death pathways. SCI samples showed elevated ERS/UPR phenotype scores that positively correlated with myeloid cell infiltration. PPI analysis pinpointed Conclusion: ERS/UPR activation is a critical component of the post-SCI transcriptomic response and is closely linked to immune remodeling.
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