Vitronectin and Its Interaction with PAI-1 Suggests a Functional Link to Vascular Changes in AMD Pathobiology
Abstract
:1. Introduction
2. Material and Methods
2.1. Description of Datasets
2.2. Association Analysis
2.3. Linear Regression Analysis of Gene Expression
2.4. Cell Culture
2.5. RNA Isolation and Reverse Transcription (RT) into Complementary DNA (cDNA)
2.6. Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR)
2.7. Expression Constructs
2.8. Purification of the Recombinant Proteins PAI-1 and Vitronectin
2.9. SDS-PAGE and Western Blot Analysis
2.10. Antibodies
2.11. Affinity Chromatography of Vitronectin Isoforms to Immobilized PAI-1
2.12. PAI-1 Activity Assay
2.13. Endogenous PAI-1 Expression and Secretion by Vascular Endothelial Cells after Exposure to Recombinant Vitronectin Isoforms
2.14. Analysis of Vitronectin-Dependent Deposition of Endogenous PAI-1 in ARPE19-Derived ECM
2.15. Statistical Analysis
3. Results
3.1. Refinement of the AMD-Associated rs704 Signal at the VTN Gene Locus by Subgroup Analysis
3.2. Functional Relationship between Vitronectin and Angiogenesis Regulator PAI-1
3.3. Genetic Variant rs704 and Vitronectin Binding to PAI-1
3.4. Genetic Variant rs704 and the Capacity of Vitronectin to Stabilize PAI-1 Activity
3.5. Vitronectin and Cellular PAI-1 Protein Expression and ECM Deposition
3.6. In Silico VTN and PAI-1 Expression Profiles
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Cases (n) | Controls (n) | OR [95% CI] | p-Value | Q-Value | |
---|---|---|---|---|---|
Early stage AMD | 6.657 | 17.832 | 0.978 [0.939–1.018] | 0.286 | 0.286 |
Late-stage AMD | 16.144 | 17.832 | 1.078 [1.044–1.113] | 3.97 × 10−6 | 1.79 × 10−5 |
Geographic atrophy (GA) | 3.235 | 17.832 | 1.048 [0.992–1.106] | 0.092 | 0.118 |
Neovascularization (NV) | 10.749 | 17.832 | 1.09 [1.052–1.13] | 2.02 × 10−6 | 1.79 × 10−5 |
Combined, GA & NV | 2.160 | 17.832 | 1.053 [0.987–1.124] | 0.120 | 0.135 |
Male | 6.532 | 7.820 | 1.084 [1.034–1.139] | 1.03 × 10−3 | 2.17 × 10−3 |
Female | 9.612 | 10.012 | 1.073 [1.027–1.119] | 1.21 × 10−3 | 2.17 × 10−3 |
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Biasella, F.; Strunz, T.; Kiel, C.; on behalf of the International AMD Genomics Consortium (IAMDGC); Weber, B.H.F.; Friedrich, U. Vitronectin and Its Interaction with PAI-1 Suggests a Functional Link to Vascular Changes in AMD Pathobiology. Cells 2022, 11, 1766. https://doi.org/10.3390/cells11111766
Biasella F, Strunz T, Kiel C, on behalf of the International AMD Genomics Consortium (IAMDGC), Weber BHF, Friedrich U. Vitronectin and Its Interaction with PAI-1 Suggests a Functional Link to Vascular Changes in AMD Pathobiology. Cells. 2022; 11(11):1766. https://doi.org/10.3390/cells11111766
Chicago/Turabian StyleBiasella, Fabiola, Tobias Strunz, Christina Kiel, on behalf of the International AMD Genomics Consortium (IAMDGC), Bernhard H. F. Weber, and Ulrike Friedrich. 2022. "Vitronectin and Its Interaction with PAI-1 Suggests a Functional Link to Vascular Changes in AMD Pathobiology" Cells 11, no. 11: 1766. https://doi.org/10.3390/cells11111766
APA StyleBiasella, F., Strunz, T., Kiel, C., on behalf of the International AMD Genomics Consortium (IAMDGC), Weber, B. H. F., & Friedrich, U. (2022). Vitronectin and Its Interaction with PAI-1 Suggests a Functional Link to Vascular Changes in AMD Pathobiology. Cells, 11(11), 1766. https://doi.org/10.3390/cells11111766