GNG7 attenuates inflammation and modulates macrophage function via the NF-κB/NLRP3 inflammasome pathways in Poly I:C-induced acute lung injury.

Authors

Fangfei Lin, Fayan Zhang, Xiaoxiao Yu, Shiming Chen, Shengyu Zhou

Published in

Biochimica et biophysica acta. Molecular basis of disease. Pages 168493. Oct 05, 2026. Epub Oct 05, 2026.

Abstract

Acute lung injury (ALI) is driven by excessive inflammation, but the molecular regulation of macrophage responses remain incompletely defined. This study investigated the role of G protein gamma subunit 7 (GNG7) in mediating inflammatory signaling in cell and mouse models of ALI. RAW264.7 macrophages were stimulated with Poly I:C and subjected to GNG7 knockdown or overexpression. Inflammatory cytokines, reactive oxygen species (ROS), phagocytic activity, and NF-κB/NLRP3 inflammasome signaling were evaluated using qRT-PCR, ELISA, fluorescence imaging and Western blotting. RNA sequencing followed by GO and KEGG analyses was performed after GNG7 knockdown. NF-κB/NLRP3 pathway involvement was examined using inhibitors BAY 11-7082 and MCC950. In vivo, Poly I:C-induced ALI mice received AAV9-sh-GNG7, followed by assessment of lung pathology, bronchoalveolar lavage fluid cytokines, and macrophage polarization markers. Poly I:C stimulation markedly upregulated GNG7 expression, whereas GNG7 knockdown caused broad transcriptomic changes enriched in virus-responsive and NOD-like receptor signaling pathways. Functional assays showed that GNG7 overexpression reduced proinflammatory cytokine production, NF-κB p65 phosphorylation, NLRP3 and ASC expression, caspase-1 activation, intracellular ROS accumulation, and neutral-red uptake, whereas GNG7 knockdown produced generally opposite changes. BAY 11-7082 and MCC950 attenuated multiple inflammatory and oxidative changes associated with GNG7 knockdown, supporting the involvement of NF-κB/NLRP3-related signaling. In mice, pulmonary GNG7 knockdown worsened lung injury, changed BALF cytokine levels toward a more inflammatory pattern, and altered CD80/CD206 marker profiles. These findings suggest that GNG7 helps limit Poly I:C induced macrophage inflammation, possibly through NF-κB/NLRP3-related signaling. Further studies are needed before GNG7 can be considered a therapeutic target for ALI.

PMID:
42833558
Bibliographic data and abstract were imported from PubMed on 06 Oct 2026.

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