Integrin β3-Mediated Cell Senescence Associates with Gut Inflammation and Intestinal Degeneration in Models of Alzheimer’s Disease
Abstract
:1. Introduction
2. Results
2.1. Age-Dependent Intestinal Tissue Degeneration in Mouse AD Models
2.2. Global Colon Protein Expression Features in 5XFAD Mice across Ages
2.3. Inflammatory Cell Infiltration into the 5XFAD Mouse Colon
2.4. Increased Integrin β3 Levels Are Associated with Cell Senescence Signatures in 5XFAD Mouse Colons
2.5. Integrin β3 Mediates APP-Induced Senescence in Colon Epithelial Cells
3. Discussion
4. Methods and Materials
4.1. Reagents and Antibodies
4.2. Cell Culturte
4.3. AD Animal Model
4.4. Label-Free Proteomics
4.5. Bioinformatics
4.6. Knowledge Graph (KG) Predictions of AD-Associated Genes
4.7. Quantitative Real Time PCR (RT-qPCR)
4.8. Western Blotting
4.9. Constructs and Transfections
4.10. H&E Staining
4.11. Alcian Blue Staining
4.12. Immunohistochemistry (IHC)
4.13. Immunofluorescence
4.14. Total Lysate Preparations
4.15. β-Galactosidase Activity Assays
4.16. RNA Interference
4.17. Statistical Analyses
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Mouse | Human | ||
---|---|---|---|
GAPDH | s-GACTTCAACAGCAACTCCCAC | GAPDH | s-GCGAGATCCCTCCAAAATCAA |
as-TCCACCACCCTGTTGCTGTA | as-GTTCACACCCATGACGAACAT | ||
P21 | s-CGAGAACGGTGGAACTTTGAC | P21 | s-TCACTGTCTTGTACCCTTGTGC |
as-CAGGGCTCAGGTAGACCTTG | as-GGCGTTTGGAGTGGTAGAAA | ||
IL-6 | s-GCTACCAAACTGGATATAATCAGGA | IL-6 | s-CAGGAGCCCAGCTATGAACT |
as-CCAGGTAGCTATGGTACTCCAGAA | as-GAAGGCAGCAGGCAACAC | ||
TNFα | s-GCCCAGGCAGTCAGATCATCT | TNFα | s-GCCCAGGCAGTCAGATCATCT |
as-TTGAGGGTTTGCTACAACATGG | as-TTGAGGGTTTGCTACAACATGG | ||
CCL2 | s-CATCCACGTGTTGGCTCA | Not tested | |
as-GATCATCTTGCTGGTGAATGAGT | |||
PAI-1 | s-GACACCCTCAGCATGTTCATC | PAI-1 | s-AGCTCCTTGTACAGATGCCG |
as-AGGGTTGCACTAAACATGTCAG | as-ACAACAGGAGGAGAAACCCA | ||
CXCL10 | s-GCTGCCGTCATTTTCTGC | CXCL10 | s-GAAAGCAGTTAGCAAGGAAAGGT |
as-TCTCACTGGCCCGTCATC | as-GACATATACTCCATGTAGGGAAGTGA |
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Tun, X.; Wang, E.J.; Gao, Z.; Lundberg, K.; Xu, R.; Hu, D. Integrin β3-Mediated Cell Senescence Associates with Gut Inflammation and Intestinal Degeneration in Models of Alzheimer’s Disease. Int. J. Mol. Sci. 2023, 24, 5697. https://doi.org/10.3390/ijms24065697
Tun X, Wang EJ, Gao Z, Lundberg K, Xu R, Hu D. Integrin β3-Mediated Cell Senescence Associates with Gut Inflammation and Intestinal Degeneration in Models of Alzheimer’s Disease. International Journal of Molecular Sciences. 2023; 24(6):5697. https://doi.org/10.3390/ijms24065697
Chicago/Turabian StyleTun, Xin, Evan J. Wang, Zhenxiang Gao, Kathleen Lundberg, Rong Xu, and Di Hu. 2023. "Integrin β3-Mediated Cell Senescence Associates with Gut Inflammation and Intestinal Degeneration in Models of Alzheimer’s Disease" International Journal of Molecular Sciences 24, no. 6: 5697. https://doi.org/10.3390/ijms24065697