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Siglec-5 suppresses LPS-induced acute lung injury via negative regulation of HSF1/SYK-mediated ROS production and pyroptosis.

Created on 15 Jul 2026

Authors

Jiwei Zhang, Weijiang Bai

Published in

Frontiers in medicine. Volume 13. Pages 1799874. Epub Jun 30, 2026.

Abstract

To investigate the protective effect of Siglec-5 on lung injury in septic mice and its molecular mechanism.
Forty-eight male SPF-grade ICR mice were randomly divided into the sham group, Model group (induced by LPS), Siglec5-OE group, and Siglec5-OE + SIRPα-OE group. After modeling, HE staining was used to evaluate pathological changes in lung tissue. ELISA was employed to measure the levels of MDA, SOD, GPX, IL-1β, IL-18, and GSDMD. RAW264.7 cells were treated with drugs, and Western blot was used to detect protein expression. Flow cytometry was performed to assess apoptosis, fluorescent probes were used to measure ROS fluorescence intensity, and immunofluorescence was used to detect NLRP3 fluorescence intensity.
Compared with the sham group, the Model group showed severe lung tissue damage, increased levels of MDA, IL-1β, IL-18, and GSDMD, and decreased levels of SOD and GPX. Compared with the Model group, the Siglec5-OE group exhibited improved lung injury, reduced levels of MDA, IL-1β, IL-18, and GSDMD, and increased levels of SOD and GPX. Compared with the Siglec5-OE group, the Siglec5-OE + SIRPα-OE group showed significantly aggravated lung tissue damage, increased levels of MDA, IL-1β, IL-18, and GSDMD, and decreased levels of SOD and GPX. In vitro experiments demonstrated that Siglec-5 promoted HSF1 protein expression, inhibited p-SYK, p-ERK, and SIRPα protein expression, thereby suppressing apoptosis, reducing ROS activity, and inhibiting NLRP3-mediated pyroptosis.
Siglec-5 inhibits LPS-induced lung injury by regulating the HSF1/SYK/ERK1/2/SIRPα signaling pathway, thereby modulating ROS and pyroptosis responses.

PMID:
42454135
Bibliographic data and abstract were imported from PubMed on 15 Jul 2026.

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