Free radical biology & medicine · 2026
Mitsugumin 53 protects against smoke inhalation lung injury via suppressing the proinflammatory response in a rat model.
СтатьяНазвание и аннотация: Перевод в очереди
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Aziz Daniel Z, Binion C Chase, Wang Xiaoliang, Xu Hai, Rodgers Skylar C, Gillis David C, Ledford Benjamin T, Siletzky Robin, Zhou Xinyu, Tsihlis Nick D, Ma Jianjie, Cai Chuanxi, Kibbe Melina R
Аннотация
OBJECTIVES: This study investigates the therapeutic potential of recombinant human Mitsugumin 53 (rhMG53) in a rodent model of smoke-induced acute lung injury (SI-ALI). We hypothesize that administration of rhMG53 will improve pulmonary function and attenuate inflammation following SI-ALI.
METHODS: Sprague Dawley rats (n = 6-9/group, 300-400 g) underwent smoke inhalation or sham. Smoke-exposed rats received intravenous rhMG53 or saline. Arterial blood gases were obtained at baseline and 2, 6, and 24 h post smoke inhalation. Lung tissue collected at 24 h was analyzed via histopathology, immunofluorescence, bulk RNA sequencing, quantitative PCR, and western blotting.
RESULTS: Six hours after smoke exposure, saline-treated rats exhibited dampened partial pressure of oxygen, whereas the rhMG53 group showed significant improvement (62.67 ± 15.81 vs. 75.83 ± 12.16 mmHg, P < .01). By 24 h, saline-treated animals remained significantly hypoxemic (79.33 mmHg, P < .01 vs. baseline), while rhMG53-treated rats recovered to baseline (87.17 mmHg), trending toward significantly higher oxygenation versus saline (P = 0.0503). Smoke-exposed saline-treated rats exhibited increased overall histopathological scores, which were reduced with rhMG53 (0.60 ± 0.17 vs. 0.37 ± 0.05, P < .01). Gene ontology analysis revealed rhMG53 mitigated smoke-induced upregulation of inflammatory response pathways. Induction of pro-inflammatory genes and elevation of NLRP3 inflammasome expression observed in smoke-exposed saline-treated lungs was significantly suppressed by rhMG53, as corroborated by qPCR and western blotting.
CONCLUSIONS: This study provides preclinical evidence for rhMG53 as a potential therapeutic for SI-ALI. RhMG53 improved oxygenation, reduced neutrophilic inflammation, and suppressed NLRP3 inflammasome activation. Further investigations in diverse models of ALI are warranted to define the therapeutic scope and translational potential of rhMG53.
METHODS: Sprague Dawley rats (n = 6-9/group, 300-400 g) underwent smoke inhalation or sham. Smoke-exposed rats received intravenous rhMG53 or saline. Arterial blood gases were obtained at baseline and 2, 6, and 24 h post smoke inhalation. Lung tissue collected at 24 h was analyzed via histopathology, immunofluorescence, bulk RNA sequencing, quantitative PCR, and western blotting.
RESULTS: Six hours after smoke exposure, saline-treated rats exhibited dampened partial pressure of oxygen, whereas the rhMG53 group showed significant improvement (62.67 ± 15.81 vs. 75.83 ± 12.16 mmHg, P < .01). By 24 h, saline-treated animals remained significantly hypoxemic (79.33 mmHg, P < .01 vs. baseline), while rhMG53-treated rats recovered to baseline (87.17 mmHg), trending toward significantly higher oxygenation versus saline (P = 0.0503). Smoke-exposed saline-treated rats exhibited increased overall histopathological scores, which were reduced with rhMG53 (0.60 ± 0.17 vs. 0.37 ± 0.05, P < .01). Gene ontology analysis revealed rhMG53 mitigated smoke-induced upregulation of inflammatory response pathways. Induction of pro-inflammatory genes and elevation of NLRP3 inflammasome expression observed in smoke-exposed saline-treated lungs was significantly suppressed by rhMG53, as corroborated by qPCR and western blotting.
CONCLUSIONS: This study provides preclinical evidence for rhMG53 as a potential therapeutic for SI-ALI. RhMG53 improved oxygenation, reduced neutrophilic inflammation, and suppressed NLRP3 inflammasome activation. Further investigations in diverse models of ALI are warranted to define the therapeutic scope and translational potential of rhMG53.