Extracellular Vesicles Secreted by Corneal Epithelial Cells Promote Myofibroblast Differentiation
Abstract
1. Introduction
2. Materials and Methods
2.1. Cell Culture
2.1.1. Human Corneal Epithelial Cells
2.1.2. Human Corneal Fibroblasts
2.1.3. Two-Dimensional (2D) Conventional Cultures
2.1.4. Three-Dimensional (3-D) Stromal Cultures
2.2. EV Isolation
2.3. EV-Labelling
2.4. Transmission Electron Microscopy (TEM) Analysis
2.5. Western Blot
2.6. Stimulated Emission Depletion (STED) Nanoscopy
2.7. Immunofluorescence Microscopy
2.8. EV Uptake
2.9. Analysis of F-Actin Organization
2.10. Collagen Contraction Assay
2.11. Proliferation Assay
2.12. Migration Assay
2.13. Proteomics
2.14. Statistical Analysis
3. Results
3.1. Characterization of Epithelial-Derived EVs
3.2. EV Uptake by hCFs
3.3. Functional Effects of hCE-TJ-Derived EVs on hCFs
3.4. EV Protein Cargo
3.5. hCE-TJ-Derived EV Protein Localization
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Pathway Name | Entitites | Reactions | ||||
---|---|---|---|---|---|---|
Found | Ratio | p-Value | FDR * | Found | Ratio | |
Formation of the ternary complex, and subsequently, the 43S complex | 28/52 | 0.005 | 1.11 × 10−16 | 3.11 × 10−15 | 3/3 | 2.44 × 10−4 |
Regulation of activated PAK-2p34 by proteasome mediated degradation | 26/50 | 0.004 | 1.11 × 10−16 | 3.11 × 10−15 | 2/2 | 1.62 × 10−4 |
AUF1 (hnRNP D0) binds and destabilizes mRNA | 29/56 | 0.005 | 1.11 × 10−16 | 3.11 × 10−15 | 4/4 | 3.25 × 10−4 |
Translation initiation complex formation | 30/59 | 0.005 | 1.11 × 10−16 | 3.11 × 10−15 | 2/2 | 1.62 × 10−4 |
Ribosomal scanning and start codon recognition | 30/59 | 0.005 | 1.11 × 10−16 | 3.11 × 10−15 | 2/2 | 1.62 × 10−4 |
Eukaryotic Translation Elongation | 42/95 | 0.008 | 1.11 × 10−16 | 3.11 × 10−15 | 9/9 | 7.31 × 10−4 |
Peptide chain elongation | 39/90 | 0.008 | 1.11 × 10−16 | 3.11 × 10−15 | 5/5 | 4.06 × 10−4 |
Formation of a pool of free 40S subunits | 43/102 | 0.009 | 1.11 × 10−16 | 3.11 × 10−15 | 2/2 | 1.62 × 10−4 |
GTP hydrolysis and joining of the 60S ribosomal subunit | 47/113 | 0.01 | 1.11 × 10−16 | 3.11 × 10−15 | 3/3 | 2.44 × 10−4 |
Nonsense-Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) | 38/96 | 0.01 | 1.11 × 10−16 | 3.11 × 10−15 | 1/1 | 8.12 × 10−5 |
Viral mRNA Translation | 37/101 | 0.009 | 1.11 × 10−16 | 3.11 × 10−15 | 2/2 | 1.62 × 10−4 |
Nonsense-Mediated Decay (NMD) | 40/117 | 0.01 | 1.11 × 10−16 | 3.11 × 10−15 | 6/6 | 4.87 × 10−4 |
Nonsense-Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) | 40/117 | 0.01 | 1.11 × 10−16 | 3.11 × 10−15 | 5/5 | 4.06 × 10−4 |
SRP-dependent cotranslational protein targeting to membrane | 37/113 | 0.01 | 1.11 × 10−16 | 3.11 × 10−15 | 5/5 | 4.06 × 10−4 |
Cap-dependent Translation Initiation | 47/120 | 0.011 | 1.11 × 10−16 | 3.11 × 10−15 | 17/18 | 0.001 |
Eukaryotic Translation Initiation | 47/120 | 0.011 | 1.11 × 10−16 | 3.11 × 10−15 | 19/21 | 0.002 |
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S | 30/60 | 0.005 | 1.11 × 10−16 | 3.11 × 10−15 | 5/6 | 4.87 × 10−4 |
Regulation of Apoptosis | 26/53 | 0.005 | 1.11 × 10−16 | 3.11 × 10−15 | 4/5 | 4.06 × 10−4 |
Eukaryotic Translation Termination | 38/94 | 0.008 | 1.11 × 10−16 | 3.11 × 10−15 | 4/5 | 4.06 × 10−4 |
Hh mutants that do not undergo autocatalytic processing are degraded by ERAD | 26/56 | 0.005 | 1.11 × 10−16 | 3.11 × 10−15 | 4/6 | 4.87 × 10−4 |
L13a-mediated translational silencing of Ceruloplasmin expression | 47/112 | 0.01 | 1.11 × 10−16 | 3.11 × 10−15 | 2/3 | 2.44 × 10−4 |
Host Interactions of HIV factors | 41/144 | 0.013 | 1.11 × 10−16 | 3.11 × 10−15 | 34/54 | 0.004 |
Translation | 67/294 | 0.026 | 1.11 × 10−16 | 3.11 × 10−15 | 57/99 | 0.008 |
Hh mutants abrogate ligand secretion | 26/59 | 0.005 | 1.11 × 10−16 | 3.11 × 10−15 | 4/7 | 5.69 × 10−4 |
Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A | 25/52 | 0.005 | 1.11 × 10−16 | 3.11 × 10−15 | 2/4 | 3.25 × 10−4 |
Protein Name | UniProt Id | Relative Protein Abundance [Average (± Stdev)] |
---|---|---|
Alanine-tRNA ligase | P49588 | 1.0 × 105 (± 2.0 × 104) |
Aminoacyl tRNA synthase complex | Q12904 | 2.2 × 104 (± 3.4 × 103) |
Asparagine-tRNA ligase | O43776 | 1.6 × 104 (± 4.1 × 103) |
Aspartate-tRNA ligase | P14868 | 5.9 × 103 (± 8.8 × 102) |
Elongation factor 1-alpha 1 | P68104 | 5.2 × 105 (± 3.6 × 104) |
Elongation factor 1-gamma | P26641 | 2.9 × 105 (± 2.3 × 104) |
Elongation factor 2 | P13639 | 3.6 × 105 (± 4.3 × 104) |
Eukaryotic translation initiation factor 3 subunit F | O00303 | 2.1 × 104 (± 4.2 × 103) |
Glycine-tRNA ligase | P41250 | 1.0 × 105 (± 9.4 × 103) |
Serine-tRNA ligase | P49591 | 1.5 × 104 (± 8.7 × 102) |
Threonine-tRNA ligase | P26639 | 2.6 × 104 (± 3.8 × 103) |
Tryptophan-tRNA ligase | P23381 | 6.4 × 103 (± 8.3 × 102) |
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McKay, T.B.; Hutcheon, A.E.K.; Zieske, J.D.; Ciolino, J.B. Extracellular Vesicles Secreted by Corneal Epithelial Cells Promote Myofibroblast Differentiation. Cells 2020, 9, 1080. https://doi.org/10.3390/cells9051080
McKay TB, Hutcheon AEK, Zieske JD, Ciolino JB. Extracellular Vesicles Secreted by Corneal Epithelial Cells Promote Myofibroblast Differentiation. Cells. 2020; 9(5):1080. https://doi.org/10.3390/cells9051080
Chicago/Turabian StyleMcKay, Tina B., Audrey E. K. Hutcheon, James D. Zieske, and Joseph B. Ciolino. 2020. "Extracellular Vesicles Secreted by Corneal Epithelial Cells Promote Myofibroblast Differentiation" Cells 9, no. 5: 1080. https://doi.org/10.3390/cells9051080
APA StyleMcKay, T. B., Hutcheon, A. E. K., Zieske, J. D., & Ciolino, J. B. (2020). Extracellular Vesicles Secreted by Corneal Epithelial Cells Promote Myofibroblast Differentiation. Cells, 9(5), 1080. https://doi.org/10.3390/cells9051080