Attenuated T cell activation and rearrangement of T cell receptor β repertoire in silica nanoparticle-induced pulmonary fibrosis of mice

Bao, Lei; Geng, Zhongfeng; Wang, Juan; Kang, Aijuan; Song, Ji‐Hyun; Huang, Xiaoyan; Zhang, Yaling; Liu, Qingping; Jiang, Tao; Pang, Yaxian; Niu, Yujie; Zhang, Rong

doi:10.1016/j.envres.2022.113678

Cited by 10 publications

(1 citation statement)

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“…Liao et al found pulmonary dysfunction in SiNPs handling workers, characterized by a decreased 25% forced expiratory flow (FEF25%) [ 2 ]. Increasing animal studies have shown that SiNPs could cause pulmonary oxidative stress, mitochondrial dysfunction, inflammation, DNA damage, and epigenetic alterations, eventually contributing to lung fibrotic lesions [ 3 – 6 ]. Nevertheless, the pathogenesis and underlying mediators remain incompletely understood, and therapeutic targets and effective treatments are lacking.…”

Section: Introductionmentioning

confidence: 99%

Epithelium-derived exosomes promote silica nanoparticles-induced pulmonary fibroblast activation and collagen deposition via modulating fibrotic signaling pathways and their epigenetic regulations

Li,

Xu,

Wang

et al. 2024

J Nanobiotechnol

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Background In the context of increasing exposure to silica nanoparticles (SiNPs) and ensuing respiratory health risks, emerging evidence has suggested that SiNPs can cause a series of pathological lung injuries, including fibrotic lesions. However, the underlying mediators in the lung fibrogenesis caused by SiNPs have not yet been elucidated. Results The in vivo investigation verified that long-term inhalation exposure to SiNPs induced fibroblast activation and collagen deposition in the rat lungs. In vitro, the uptake of exosomes derived from SiNPs-stimulated lung epithelial cells (BEAS-2B) by fibroblasts (MRC-5) enhanced its proliferation, adhesion, and activation. In particular, the mechanistic investigation revealed SiNPs stimulated an increase of epithelium-secreted exosomal miR-494-3p and thereby disrupted the TGF-β/BMPR2/Smad pathway in fibroblasts via targeting bone morphogenetic protein receptor 2 (BMPR2), ultimately resulting in fibroblast activation and collagen deposition. Conversely, the inhibitor of exosomes, GW4869, can abolish the induction of upregulated miR-494-3p and fibroblast activation in MRC-5 cells by the SiNPs-treated supernatants of BEAS-2B. Besides, inhibiting miR-494-3p or overexpression of BMPR2 could ameliorate fibroblast activation by interfering with the TGF-β/BMPR2/Smad pathway. Conclusions Our data suggested pulmonary epithelium-derived exosomes serve an essential role in fibroblast activation and collagen deposition in the lungs upon SiNPs stimuli, in particular, attributing to exosomal miR-494-3p targeting BMPR2 to modulate TGF-β/BMPR2/Smad pathway. Hence, strategies targeting exosomes could be a new avenue in developing therapeutics against lung injury elicited by SiNPs. Graphical Abstract

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Section: Introductionmentioning

confidence: 99%