Effects of Cilostazol on Angiogenesis in Diabetes through Adiponectin/Adiponectin Receptors/Sirtuin1 Signaling Pathway
Abstract
:1. Introduction
2. Results
2.1. Cilostazol Increased Adiponectin Levels in ECs by Stimulating Their Production from SMCs
2.2. Cilostazol Increased Angiogenic Functions by Upregulating the Expression of Adiponectin Receptors and Enhancing Adiponectin Released from SMCs by Binding to Adiponectin Receptors in HUVECs
2.3. Cilostazol Enhanced SIRT/AMPK Signaling in HUVECs
2.4. Contributions of SIRT to the Cilostazol-Induced Angiogenic Effects
2.5. The Angiogenic Effects of Cilostazol were Mediated by AdipoRs In Vivo
3. Discussion
4. Materials and Methods
4.1. Reagents
4.2. Cell Culture
4.3. Transwell Coculture Experiments
4.4. Immunofluorescence Staining
4.5. Enzyme-Linked Immunosorbent Assay (ELISA)
4.6. Short Hairpin RNA (shRNA) Transfection
4.7. Proliferation Assay
4.8. Migration Assay
4.9. Matrigel Tube Formation
4.10. Analysis of Apoptosis
4.11. Measurement of Nitric Oxide Production
4.12. RNA Isolation, Reverse Transcription, and Real-Time PCR
4.13. Western Blot Analysis
4.14. Diabetic Mice and Murine Hindlimb Ischemia Model
4.15. Knockdown of adipoR1 and adipoR2 in the Hindlimb
4.16. Laser Doppler Flow Imaging
4.17. Measurement of Capillary Density in Ischemic Limbs
4.18. Enumeration of Circulating Progenitor Cells
4.19. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Tseng, S.-Y.; Chang, H.-Y.; Li, Y.-H.; Chao, T.-H. Effects of Cilostazol on Angiogenesis in Diabetes through Adiponectin/Adiponectin Receptors/Sirtuin1 Signaling Pathway. Int. J. Mol. Sci. 2022, 23, 14839. https://doi.org/10.3390/ijms232314839
Tseng S-Y, Chang H-Y, Li Y-H, Chao T-H. Effects of Cilostazol on Angiogenesis in Diabetes through Adiponectin/Adiponectin Receptors/Sirtuin1 Signaling Pathway. International Journal of Molecular Sciences. 2022; 23(23):14839. https://doi.org/10.3390/ijms232314839
Chicago/Turabian StyleTseng, Shih-Ya, Hsien-Yuan Chang, Yi-Heng Li, and Ting-Hsing Chao. 2022. "Effects of Cilostazol on Angiogenesis in Diabetes through Adiponectin/Adiponectin Receptors/Sirtuin1 Signaling Pathway" International Journal of Molecular Sciences 23, no. 23: 14839. https://doi.org/10.3390/ijms232314839