GP130 Regulates Macrophage Polarization and Functional Recovery after Spinal Cord Injury in Rats: A Single-Cell RNA Sequencing Study.

Authors

Mengqi Gao, Danfen Zhang, Mingze Liu, Yezhong Wang, Yanbin Ke

Published in

Inflammation. Jul 15, 2026. Epub Jul 15, 2026.

Abstract

Neuroinflammation and macrophage polarization play important roles in secondary injury and functional recovery after spinal cord injury (SCI). GP130, the common signal-transducing receptor subunit of the IL-6 cytokine family, is closely associated with JAK/STAT3-mediated inflammatory signaling. However, its role in macrophage polarization after SCI remains unclear. This study investigated whether GP130 inhibition regulates macrophage polarization and improves functional recovery after SCI. A rat model of T10 spinal cord compression injury was established using a standardized microvascular clip compression method. The GP130 inhibitor SC144 was administered after SCI. Functional recovery was evaluated using BBB scoring and inclined plane tests. Histopathological, ultrastructural, immunofluorescence, flow cytometry, qRT-PCR, western blotting, ELISA, and single-cell RNA sequencing analyses were performed to evaluate tissue injury, inflammatory signaling, and macrophage polarization. Primary bone marrow-derived macrophages were further used to assess the direct effects of GP130 knockdown or pharmacological inhibition on macrophage phenotype in vitro. SCI induced severe locomotor impairment, tissue disruption, ultrastructural damage, and activation of GP130-related inflammatory signaling. SC144 treatment improved functional recovery, reduced inflammatory cytokine expression, and attenuated downstream STAT3 activation. Single-cell RNA sequencing revealed a prominent monocyte/macrophage-related myeloid-cell response after SCI and transcriptional heterogeneity within the myeloid compartment. Immunofluorescence and flow cytometry showed that GP130 inhibition reduced M1-like marker expression and promoted M2-like marker expression in vivo. In primary macrophages, GP130-siRNA and SC144 similarly suppressed M1-like pro-inflammatory marker expression and enhanced M2-like reparative marker expression. GP130 inhibition modulates macrophage polarization and promotes functional recovery after T10 spinal cord compression injury. These findings suggest that GP130-related inflammatory signaling may be a potential therapeutic target for regulating macrophage-mediated neuroinflammation after SCI.

PMID:
42455195
Bibliographic data and abstract were imported from PubMed on 15 Jul 2026.

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