Abnormal Lysosomal Positioning and Small Extracellular Vesicle Secretion in Arterial Stiffening and Calcification of Mice Lacking Mucolipin 1 Gene
Abstract
:1. Introduction
2. Results
2.1. Characterization of Mucolipin 1 (Mcoln1) Gene KO Mice
2.2. Mcoln1 Gene Deletion Enhanced Arterial Medial Calcification in Vit D-Treated Mice
2.3. Arterial Medial SMC Phenotypic Transition in Vit D-Treated Mcoln1−/− Mice
2.4. ALG-2 and Rab7 Interact with the Lysosome to Mediate Mcoln1-Dependent Lysosome Coupling in Aortic Medial SMCs in Vit D-Treated Mcoln1−/− Mice
2.5. Mcoln1 Gene Deletion Elevated sEV Secretion by Inhibiting Lysosomes and MVB Interactions in the Arterial Medial Calcification
2.6. Role of Mcoln1 in sEV Release in the Arterial Medial Calcification
2.7. Lysosome–MVB Interactions and sEV Release Controlled by TRPML1 Signaling Pathway in Coronary Artery Smooth Muscle Cells (CASMCs)
2.8. Mcoln1 Gene Deletion Accelerates Arterial Stiffness
3. Discussion
4. Material and Methods
4.1. Reagents and Antibodies
4.2. Primary Culture of Mouse CASMCs
4.3. Animal Model
4.4. Alizarin Red S Staining
4.5. Calcium Assay
4.6. Immunohistochemical Analyses
4.7. Immunofluorescent Staining
4.8. Nanoparticle Tracking Analysis (NTA)
4.9. Real Time-PCR Studies
4.10. Western Blot Analysis
4.11. Non-Invasive, in Vivo Measurement of Aortic Pulse Wave Velocity (PWV)
4.12. Elastin Staining
4.13. Statistical Analysis
Author Contributions
Acknowledgments
Conflicts of Interest
References
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Bhat, O.M.; Yuan, X.; Camus, S.; Salloum, F.N.; Li, P.-L. Abnormal Lysosomal Positioning and Small Extracellular Vesicle Secretion in Arterial Stiffening and Calcification of Mice Lacking Mucolipin 1 Gene. Int. J. Mol. Sci. 2020, 21, 1713. https://doi.org/10.3390/ijms21051713
Bhat OM, Yuan X, Camus S, Salloum FN, Li P-L. Abnormal Lysosomal Positioning and Small Extracellular Vesicle Secretion in Arterial Stiffening and Calcification of Mice Lacking Mucolipin 1 Gene. International Journal of Molecular Sciences. 2020; 21(5):1713. https://doi.org/10.3390/ijms21051713
Chicago/Turabian StyleBhat, Owais M., Xinxu Yuan, Sarah Camus, Fadi N. Salloum, and Pin-Lan Li. 2020. "Abnormal Lysosomal Positioning and Small Extracellular Vesicle Secretion in Arterial Stiffening and Calcification of Mice Lacking Mucolipin 1 Gene" International Journal of Molecular Sciences 21, no. 5: 1713. https://doi.org/10.3390/ijms21051713