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Topical rapamycin systematically suppresses the early stages of pulsed dye laser-induced angiogenesis pathways
Lin Gao1, Sydney Phan, Dawnica Mercado Nadora
1Department of Surgery and Biomedical Engineering, Beckman Laser Institute and Medical Clinic, University of California, Irvine, 92612, California; Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
Background:
Administration of topical rapamycin (RPM) suppresses the regeneration and revascularization of photocoagulated blood vessels induced by pulsed dye laser (PDL).
Objective:
To systematically elucidate the molecular pathophysiology of the inhibition of PDL-induced angiogenesis by topical RPM in a rodent model.
Methods:
The mRNA expression profiles of 86 angiogenic genes and phosphorylation levels of ribosomal protein S6 kinase (P70S6K) in rodent skin were examined with or without topical RPM administration post-PDL exposure.
Results:
The PDL-induced systematic increases in transcriptional levels of angiogenic genes showed a peak expression at days 3-7 post-PDL in rodent skin. Topical application of 1% RPM significantly and systematically suppressed the PDL-induced increase in mRNA levels of the examined angiogenic genes during the first five days post-PDL. The phosphorylation levels of P70S6K increased after PDL exposure but those increases were suppressed by the topical RPM. After topical application, RPM penetrated to an approximate depth of 768.4 μm into rodent skin.
Conclusion:
Topical application of 1% RPM can significantly and systematically suppress the PDL-induced early stage of angiogenesis via inhibition of the AKT/mTOR/P70S6K pathway in a rodent model.
Insights
Topical rapamycin (RPM) suppresses new blood vessel formation after laser treatment. This study reveals RPM inhibits key molecular pathways involved in angiogenesis, offering insights into wound healing and vascular regeneration.
Area of Science:
- Dermatology
- Molecular Biology
- Vascular Biology
Background:
- Topical rapamycin (RPM) is known to inhibit blood vessel regeneration after pulsed dye laser (PDL) treatment.
- The exact molecular mechanisms behind this suppression are not fully understood.
Purpose of the Study:
- To investigate the molecular pathophysiology of how topical RPM inhibits PDL-induced angiogenesis.
- To elucidate the role of specific gene expression and protein phosphorylation in this process.
Main Methods:
- Analysis of mRNA expression profiles for 86 angiogenic genes in rodent skin post-PDL exposure.
- Measurement of ribosomal protein S6 kinase (P70S6K) phosphorylation levels.
- Assessment of topical RPM penetration depth in rodent skin.
Main Results:
- PDL-induced angiogenic gene expression peaked at 3-7 days post-treatment.
- Topical RPM significantly suppressed angiogenic gene mRNA levels within the first five days.
- PDL exposure increased P70S6K phosphorylation, which was inhibited by topical RPM.
- RPM penetrated approximately 768.4 μm into the skin.
Conclusions:
- Topical RPM effectively suppresses early-stage angiogenesis induced by PDL.
- The mechanism involves the inhibition of the AKT/mTOR/P70S6K signaling pathway.
- Findings provide a deeper understanding of RPM's effects on vascular regeneration.
