Thy-1 dependent uptake of mesenchymal stem cell-derived extracellular vesicles blocks myofibroblastic differentiation

Autor: James S. Hagood, Simon S. Wong, Shu Chien, Chunting Tan, Joy M. Chan, Tzu-Pin Shentu, Celia R. Espinoza, Mateja Cernelc-Kohan, Irene Gramaglia, Tse-Shun Huang, Henri C. van der Heyde
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Integrin
lcsh:Medicine
Lung injury
CDH2
Autoimmune Disease
Article
Transforming Growth Factor beta1
Extracellular Vesicles
03 medical and health sciences
Idiopathic pulmonary fibrosis
Paracrine signalling
Rare Diseases
Pulmonary fibrosis
medicine
Humans
Myofibroblasts
Fibroblast
lcsh:Science
Lung
Multidisciplinary
biology
Chemistry
Mesenchymal stem cell
lcsh:R
Cell Differentiation
Mesenchymal Stem Cells
Fibroblasts
respiratory system
Stem Cell Research
medicine.disease
Idiopathic Pulmonary Fibrosis
3. Good health
respiratory tract diseases
Other Physical Sciences
030104 developmental biology
medicine.anatomical_structure
Respiratory
Cancer research
biology.protein
Thy-1 Antigens
Stem Cell Research - Nonembryonic - Non-Human
lcsh:Q
Biochemistry and Cell Biology
Biotechnology
Zdroj: Shentu, Tzu-Pin; Huang, Tse-Shun; Cernelc-Kohan, Mateja; Chan, Joy; Wong, Simon S; Espinoza, Celia R; et al.(2017). Thy-1 dependent uptake of mesenchymal stem cell-derived extracellular vesicles blocks myofibroblastic differentiation.. Scientific reports, 7(1), 18052. doi: 10.1038/s41598-017-18288-9. UC San Diego: Retrieved from: http://www.escholarship.org/uc/item/6522p939
Scientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
Scientific Reports
Scientific reports, vol 7, iss 1
Popis: Bone marrow-derived mesenchymal stem cells (MSC) have been promoted for multiple therapeutic applications. Many beneficial effects of MSCs are paracrine, dependent on extracellular vesicles (EVs). Although MSC-derived EVs (mEVs) are beneficial for acute lung injury and pulmonary fibrosis, mechanisms of mEV uptake by lung fibroblasts and their effects on myofibroblastic differentiation have not been established. We demonstrate that mEVs, but not fibroblast EVs (fEVs), suppress TGFβ1-induced myofibroblastic differentiation of normal and idiopathic pulmonary fibrosis (IPF) lung fibroblasts. MEVs display increased time- and dose-dependent cellular uptake compared to fEVs. Removal or blocking of Thy-1, or blocking Thy-1-beta integrin interactions, decreased mEV uptake and prevented suppression of myofibroblastic differentiation. MicroRNAs (miRs) 199a/b-3p, 21-5p, 630, 22-3p, 196a-5p, 199b-5p, 34a-5p and 148a-3p are selectively packaged in mEVs. In silico analyses indicated that IPF lung fibroblasts have increased expression of genes that are targets of mEV-enriched miRs. MiR-630 mimics blocked TGFβ1 induction of CDH2 in normal and IPF fibroblasts, and antagomiR-630 abrogated the effect of mEV on CDH2 expression. These data suggest that the interaction of Thy-1 with beta integrins mediates mEV uptake by lung fibroblasts, which blocks myofibroblastic differentiation, and that mEVs are enriched for miRs that target profibrotic genes up-regulated in IPF fibroblasts.
Databáze: OpenAIRE
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