Extracellular Vesicles from Fibroblasts Induce Epithelial-Cell Senescence in Pulmonary Fibrosis
| العنوان: | Extracellular Vesicles from Fibroblasts Induce Epithelial-Cell Senescence in Pulmonary Fibrosis |
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| المؤلفون: | Souichiro Suzuki, Kazuma Kishi, Takahiro Ochiya, Atsushi Miyamoto, Jun Araya, Tadasu Kohno, Tsukasa Kadota, Yusuke Yoshioka, Yu Fujita, Shunsuke Minagawa, Takeshi Fujii, Hiromichi Hara, Kazuyoshi Kuwano, Sakashi Fujimori |
| المصدر: | American Journal of Respiratory Cell and Molecular Biology. 63:623-636 |
| بيانات النشر: | American Thoracic Society, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Pulmonary and Respiratory Medicine, Senescence, DNA damage, Chemistry, Clinical Biochemistry, Cell Biology, respiratory system, medicine.disease, Exosome, humanities, respiratory tract diseases, 03 medical and health sciences, Idiopathic pulmonary fibrosis, Paracrine signalling, 030104 developmental biology, 0302 clinical medicine, medicine.anatomical_structure, 030228 respiratory system, Fibrosis, Pulmonary fibrosis, medicine, Cancer research, Fibroblast, Molecular Biology |
| الوصف: | Aberrant epithelial-mesenchymal interactions have critical roles in regulating fibrosis development. The involvement of extracellular vesicles (EVs), including exosomes, remains to be elucidated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Here, we found that lung fibroblasts (LFs) from patients with IPF induce cellular senescence via EV-mediated transfer of pathogenic cargo to lung epithelial cells. Mechanistically, IPF LF-derived EVs increased mitochondrial reactive oxygen species and associated mitochondrial damage in lung epithelial cells, leading to activation of the DNA damage response and subsequent epithelial-cell senescence. We showed that IPF LF-derived EVs contain elevated levels of microRNA-23b-3p (miR-23b-3p) and miR-494-3p, which suppress SIRT3, resulting in the epithelial EV-induced phenotypic changes. Furthermore, the levels of miR-23b-3p and miR-494-3p found in IPF LF-derived EVs correlated positively with IPF disease severity. These findings reveal that the accelerated epithelial-cell mitochondrial damage and senescence observed during IPF pathogenesis are caused by a novel paracrine effect of IPF fibroblasts via microRNA-containing EVs. |
| تدمد: | 1535-4989 1044-1549 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::f8ae09fb1aceb5590fa9f4b54180a5cdTest https://doi.org/10.1165/rcmb.2020-0002ocTest |
| رقم الانضمام: | edsair.doi...........f8ae09fb1aceb5590fa9f4b54180a5cd |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15354989 10441549 |
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