1. Nebulized milk exosomes loaded with siTGF-β1 ameliorate pulmonary fibrosis by inhibiting EMT pathway and enhancing collagen permeability.
- Author
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Qiu, Chong, Zhao, Zhenyu, Xu, Chenglin, Yuan, Ranran, Ha, Yuxuan, Tu, Qingchao, Zhang, Houqian, Mu, Zhen, Xin, Quanlin, Tian, Yu, Wang, Aiping, Wang, Hongbo, and Shi, Yanan
- Subjects
PULMONARY fibrosis ,EPITHELIAL-mesenchymal transition ,EXOSOMES ,PERMEABILITY ,INTERSTITIAL lung diseases - Abstract
Pulmonary Fibrosis (PF) is a fatal disease in the interstitial lung associated with high mortality, morbidity, and poor prognosis. Transforming growth factor-β1 (TGF-β1) is a fibroblast-activating protein that promotes fibrous diseases. Herein, an inhalable system was first developed using milk exosomes (M-Exos) encapsulating siRNA against TGF-β1 (MsiTGF-β1), and their therapeutic potential for bleomycin (BLM)-induced PF was investigated. M-siTGF-β1 was introduced into the lungs of mice with PF through nebulization. The collagen penetration effect and lysosomal escape ability were verified in vitro. Inhaled MsiTGF-β1 notably alleviated inflammatory infiltration, attenuated extracellular matrix (ECM) deposition, and increased the survival rate of PF mice by 4.7-fold. M-siTGF-β1 protected lung tissue from BLM toxicity by efficiently delivering specific siRNA to the lungs, leading to TGF-β1 mRNA silencing and epithelial mesenchymal transition pathway inhibition. Therefore, M-siTGF-β1 offers a promising avenue for therapeutic intervention in fibrosis-related disorders. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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