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Updated: Jul 15, 2025

Induction of Adhesion-dependent Signals Using Low-intensity Ultrasound
Published on: May 8, 2012
High-Intensity Focused Ultrasound Increases Collagen and Elastin Fiber Synthesis by Modulating Caveolin-1 in Aging
Seyeon Oh1, Do-Young Rhee2, Sosorburam Batsukh1,3
1Functional Cellular Networks Laboratory, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine, Incheon 21999, Republic of Korea.
Abstract:
Caveolin-1 (Cav-1) induces cellular senescence by reducing extracellular signal-regulated kinase (ERK)1/2 phosphorylation and activating p53 via inhibition of mouse double minute 2 homolog (MDM2) and sirtuin 1 (Sirt1), promoting cell cycle arrest and decreasing fibroblast proliferation and collagen synthesis. High-intensity focused ultrasound (HIFU) treatment increases collagen synthesis, rejuvenating skin. Using H2O2-induced senescent fibroblasts and the skin of 12-month-old mice, we tested the hypothesis that HIFU increases collagen production through Cav-1 modulation. HIFU was administered at 0.3, 0.5, or 0.7 J in the LINEAR and DOT modes. In both models, HIFU administration decreased Cav-1 levels, increased ERK1/2 phosphorylation, and decreased the binding of Cav-1 with both MDM2 and Sirt1. HIFU administration decreased p53 activation (acetylated p53) and p21 levels and increased cyclin D1, cyclin-dependent kinase 2, and proliferating cell nuclear antigen levels in both models. HIFU treatment increased collagen and elastin expression, collagen fiber accumulation, and elastin fiber density in aging skin, with 0.5 J in LINEAR mode resulting in the most prominent effects. HIFU treatment increased collagen synthesis to levels similar to those in Cav-1-silenced senescent fibroblasts. Our results suggest that HIFU administration increases dermal collagen and elastin fibers in aging skin via Cav-1 modulation and reduced p53 activity.
Insights
High-intensity focused ultrasound (HIFU) rejuvenates aging skin by reducing caveolin-1 (Cav-1) and p53 activity, boosting collagen and elastin production. This HIFU-induced skin rejuvenation enhances fibroblast proliferation and collagen synthesis.
Area of Science:
- Dermatology
- Cell Biology
- Biomedical Engineering
Background:
- Cellular senescence, driven by caveolin-1 (Cav-1), impairs skin aging by reducing fibroblast proliferation and collagen synthesis.
- High-intensity focused ultrasound (HIFU) is known to promote skin rejuvenation and increase collagen production.
Purpose of the Study:
- To investigate the mechanism by which HIFU enhances collagen production in senescent skin.
- To determine if HIFU modulates caveolin-1 (Cav-1) levels and related signaling pathways.
Main Methods:
- Utilized H2O2-induced senescent fibroblasts and aged mouse skin models.
- Administered HIFU at varying energy levels (0.3, 0.5, 0.7 J) and modes (LINEAR, DOT).
- Assessed Cav-1 levels, ERK1/2 phosphorylation, p53 activation, cell cycle markers, and collagen/elastin expression.
Main Results:
- HIFU treatment decreased Cav-1 levels and its binding with MDM2 and Sirt1.
- HIFU increased ERK1/2 phosphorylation, reduced p53 activation and p21 levels, and elevated cell proliferation markers.
- Significant increases in collagen and elastin expression and density were observed, with 0.5 J in LINEAR mode being most effective.
Conclusions:
- HIFU administration rejuvenates aging skin by modulating Cav-1, thereby reducing p53 activity and promoting collagen and elastin synthesis.
- HIFU's mechanism involves downregulating Cav-1, enhancing ERK1/2 signaling, and inhibiting the senescence pathway.
- The findings support HIFU as a therapeutic strategy for skin aging and collagenesis.
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