Activation of Sirt1 protects from single-walled carbon nanotubes-induced pulmonary fibrosis by inhibiting alveolar macrophage senescence
Purpose: Expanding industrial applications of carbon nanotube (CNT) have led to the concern for the increased risk of pulmonary fibrosis. The current study investigated the role of alveolar macrophages (AMs) senescence during single-walled CNT (SWCNT)-provoked pulmonary fibrosis and the underlying m...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-09-01
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| Series: | Ecotoxicology and Environmental Safety |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651325009741 |
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| Summary: | Purpose: Expanding industrial applications of carbon nanotube (CNT) have led to the concern for the increased risk of pulmonary fibrosis. The current study investigated the role of alveolar macrophages (AMs) senescence during single-walled CNT (SWCNT)-provoked pulmonary fibrosis and the underlying mechanism. Methods: Mice were intratracheally instilled with 40 μg SWCNT, then sacrificed on days 1, 7 and 28 post administration. In vitro, primary AMs from mice were stimulated with 10 μg/ml SWCNT for different time points (6, 12 and 24 h). Next, silent information regulator 1 (Sirt1) siRNA intervene was performed based on in vitro and in vivo to clarify the mechanism of SWCNT-induced AMs senescence. Sirt1 activator SRT 1720 treatment was used to determine its therapeutic potential for SWCNT-induced pulmonary fibrosis. Results: In vivo experiments manifested that SWCNT exposure promoted oxidative stress in lungs and AMs senescence, and accelerated AMs senescence was closely associated with SWCNT-provoked pulmonary fibrosis. In vitro experiments, the time-dependent effect of SWCNT treatment on AMs senescence accompanied with elevated pro-fibrotic senescence-associated secretory phenotype (SASP) secretion was observed. Notably, SWCNT exposure down-regulated Sirt1 expression in AMs during the stage of pulmonary fibrosis. Inhibiting Sirt1 aggravated SWCNT-induced pulmonary fibrosis via promoting AMs senescence and SASP secretion. Importantly, activating Sirt1 using SRT 1720 effectively alleviated SWCNT-provoked pulmonary fibrosis via inhibiting AMs senescence. Conclusion: Our study reveals that Sirt1-dependent AMs senescence regulates SWCNT-provoked pulmonary fibrosis, and activation of Sirt1 could be a promising therapeutic target. |
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| ISSN: | 0147-6513 |