Exosomal miRNA Let-7 from Menstrual Blood-Derived Endometrial Stem Cells Alleviates Pulmonary Fibrosis through Regulating Mitochondrial DNA Damage
Joint Authors
Lin, Yiping
Jin, Juan
Wang, Yunguang
Feng, Wei
Sun, Lifang
Zhu, Min
Yin, Jia
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-17, 17 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-12-17
Country of Publication
Egypt
No. of Pages
17
Main Subjects
Abstract EN
Idiopathic pulmonary fibrosis (IPF) is a prototype of chronic, progressive, and fibrotic lung disease with high morbidity and high mortality.
Menstrual blood-derived stem cells (MenSCs) have proven to be an attractive tool for the treatment of acute lung injury and fibrosis-related diseases through immunosuppression and antifibrosis.
However, whether MenSC-derived exosomes have the similar function on pulmonary fibrosis remains unclear.
In the present study, exosomes secreted from MenSCs (MenSCs-Exo) were verified by transmission electron microscope (TEM), nanoparticle tracking analyzer (NTA), and western blotting.
And MenSC-Exo addition significantly improved BLM-induced lung fibrosis and alveolar epithelial cell damage in mice, mainly reflected in BLM-mediated enhancement of the fibrosis score, blue collagen deposition, dry/wet gravity ratio, hydroxyproline and malondialdehyde levels, and downregulation of glutathione peroxidase, which were all robustly reversed by MenSC-Exo management.
Additionally, BLM- and TGF-β1-evoked cellular reactive oxygen species (ROS), mitochondrial DNA (mtDNA) damage, and cell apoptosis were rescued by MenSCs-Exo in vivo and in vitro.
Further study indicated that the MenSCs-Exo could transport miRNA Let-7 into recipient alveolar epithelial cells.
Let-7 inhibitor administration significantly blocked the exosome-mediated improvement role on lung fibrosis in mice.
Mechanistically, Let-7 was able to regulate the expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX1) through binding to its 3′-UTR region.
Forced expression of LOX1 promoted the expression of apoptosis-related protein and mtDNA damage markers via regulating NLRP3 which was also confirmed in BLM model mice under the combination therapy of the exosome and Let-7 inhibitor.
Collectively, this study demonstrates that exosomal Let-7 from MenSCs remits pulmonary fibrosis through regulating ROS, mtDNA damage, and NLRP3 inflammasome activation.
This provides a new approach of exocytosis on the treatment of fibrotic lung disease.
American Psychological Association (APA)
Sun, Lifang& Zhu, Min& Feng, Wei& Lin, Yiping& Yin, Jia& Jin, Juan…[et al.]. 2019. Exosomal miRNA Let-7 from Menstrual Blood-Derived Endometrial Stem Cells Alleviates Pulmonary Fibrosis through Regulating Mitochondrial DNA Damage. Oxidative Medicine and Cellular Longevity،Vol. 2019, no. 2019, pp.1-17.
https://search.emarefa.net/detail/BIM-1203585
Modern Language Association (MLA)
Sun, Lifang…[et al.]. Exosomal miRNA Let-7 from Menstrual Blood-Derived Endometrial Stem Cells Alleviates Pulmonary Fibrosis through Regulating Mitochondrial DNA Damage. Oxidative Medicine and Cellular Longevity No. 2019 (2019), pp.1-17.
https://search.emarefa.net/detail/BIM-1203585
American Medical Association (AMA)
Sun, Lifang& Zhu, Min& Feng, Wei& Lin, Yiping& Yin, Jia& Jin, Juan…[et al.]. Exosomal miRNA Let-7 from Menstrual Blood-Derived Endometrial Stem Cells Alleviates Pulmonary Fibrosis through Regulating Mitochondrial DNA Damage. Oxidative Medicine and Cellular Longevity. 2019. Vol. 2019, no. 2019, pp.1-17.
https://search.emarefa.net/detail/BIM-1203585
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1203585