首页|Exosome-encapsulated IncRNA HOTAIRM1 contributes to PM2.5-aggravated COPD airway remodeling by enhancing myofibroblast differentiation
Exosome-encapsulated IncRNA HOTAIRM1 contributes to PM2.5-aggravated COPD airway remodeling by enhancing myofibroblast differentiation
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Emphysema,myofibroblast accumulation and airway remodeling can occur in the lungs due to exposure to atmospheric pollution,especially fine particulate matter(PM2.5),leading to chronic obstructive pulmonary disease(COPD).Specifically,bronchial epithelium-fibroblast communication participates in airway remodeling,which results in COPD.An increasing number of studies are now being conducted on the role of exosome-mediated cell-cell communication in disease pathogenesis.Here,we investigated whether exosomes generated from bronchial epithelial cells could deliver information to normal stromal fibroblasts and provoke cellular responses,resulting in airway obstruction in COPD.We studied the mechanism of exosome-mediated intercellular communication between human bronchial epithelial(HBE)cells and primary lung fibroblasts(pLFs).We found that PM2.5-induced HBE-derived exosomes promoted myofibroblast differentiation in pLFs.Then,the exosomal lncRNA expression profiles derived from PM2.5-treated HBE cells and nontreated HBE cells were investigated using an Agilent Human LncRNA Array.Combining coculture assays and direct exosome treatment,we found that HBE cell-derived exosomal HOTAIRM1 facilitated the myofibroblast differentiation of pLFs.Surprisingly,we discovered that exosomal HOTAIRM1 enhanced pLF proliferation to secrete excessive collagen secretion,leading to airway obstruction by stimulating the TGF-β/SMAD3 signaling pathway.Significantly,PM2.5 reduced FEV1/FVC and FEV1 and increased the level of serum exosomal HOTAIRM1 in healthy people;moreover,serum exosomal HOTAIRM1 was associated with PM2.5-related reductions in FEV1/FVC and FVC.These findings show that PM2.5 triggers al-terations in exosome components and clarify that one of the paracrine mediators of myofibroblast differentiation is bronchial epithelial cell-derived HOTAIRM1,which has the potential to be an effective prevention and therapeutic target for PM2.5-induced COPD.
Huaqi Guo、Luo Fei、Hengyi Yu、Yan Li、Yan Feng、Shaowei Wu、Yan Wang
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The Ninth People's Hospital of Shanghai Jiao Tong University School of Medicine,Shanghai 200011,China
School of Public Health,Shanghai Jiao Tong University School of Medicine,Shanghai 200020,China
Department of Occupational and Environmental Health Sciences,School of Public Health,Xi'an Jiao Tong University Health Science Center,Xi'an 710049,China
National Natural Science Foundation of ChinaNational Natural Science Foundation of China
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