» Articles » PMID: 38867284

Epithelium-derived Exosomes Promote Silica Nanoparticles-induced Pulmonary Fibroblast Activation and Collagen Deposition Via Modulating Fibrotic Signaling Pathways and Their Epigenetic Regulations

Overview
Publisher Biomed Central
Specialty Biotechnology
Date 2024 Jun 12
PMID 38867284
Authors
Affiliations
Soon will be listed here.
Abstract

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.

Citing Articles

Proteome-wide mendelian randomization identifies causal plasma proteins in interstitial lung disease.

Yu K, Li W, Long W, Li Y, Li Y, Liao H Sci Rep. 2025; 15(1):2293.

PMID: 39824903 PMC: 11748740. DOI: 10.1038/s41598-025-85338-y.


Lung Single-Cell Transcriptomics Offers Insights into the Pulmonary Interstitial Toxicity Caused by Silica Nanoparticles.

Li Y, Yao Q, Xu H, Ren J, Zhu Y, Guo C Environ Health (Wash). 2024; 2(11):786-801.

PMID: 39568699 PMC: 11574632. DOI: 10.1021/envhealth.4c00052.

References
1.
Yu X, Odenthal M, Fries J . Exosomes as miRNA Carriers: Formation-Function-Future. Int J Mol Sci. 2016; 17(12). PMC: 5187828. DOI: 10.3390/ijms17122028. View

2.
Dinh P, Paudel D, Brochu H, Popowski K, Gracieux M, Cores J . Inhalation of lung spheroid cell secretome and exosomes promotes lung repair in pulmonary fibrosis. Nat Commun. 2020; 11(1):1064. PMC: 7048814. DOI: 10.1038/s41467-020-14344-7. View

3.
Guo C, Xia Y, Niu P, Jiang L, Duan J, Yu Y . Silica nanoparticles induce oxidative stress, inflammation, and endothelial dysfunction in vitro via activation of the MAPK/Nrf2 pathway and nuclear factor-κB signaling. Int J Nanomedicine. 2015; 10:1463-77. PMC: 4345992. DOI: 10.2147/IJN.S76114. View

4.
Qin X, Lin X, Liu L, Li Y, Li X, Deng Z . Macrophage-derived exosomes mediate silica-induced pulmonary fibrosis by activating fibroblast in an endoplasmic reticulum stress-dependent manner. J Cell Mol Med. 2021; 25(9):4466-4477. PMC: 8093963. DOI: 10.1111/jcmm.16524. View

5.
Bisserier M, Mathiyalagan P, Zhang S, Elmastour F, Dorfmuller P, Humbert M . Regulation of the Methylation and Expression Levels of the BMPR2 Gene by SIN3a as a Novel Therapeutic Mechanism in Pulmonary Arterial Hypertension. Circulation. 2021; 144(1):52-73. PMC: 8293289. DOI: 10.1161/CIRCULATIONAHA.120.047978. View