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Human Ex vivo Wound Model and Whole-Mount Staining Approach to Accurately Evaluate Skin Repair
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Compressive Forces Induce Epigenetic Activation of Aged Human Dermal Fibroblasts Through ERK Signaling Pathway
Hui Liu1,2, Luezhen Yuan1,2,3, Lucrezia Baldi2
1Division of Biology and Chemistry, Paul Scherrer Institut, Villigen, Switzerland.
Aging Cell
|March 13, 2025
Summary
Applying compressive force rejuvenates aged human dermal fibroblasts (HDFs) by triggering epigenetic changes via the ERK pathway. This cellular rejuvenation enhances wound healing and skin regeneration potential.
Area of Science:
- Cell Biology
- Epigenetics
- Dermatology
Background:
- Aging in human dermal fibroblasts (HDFs) impairs skin function and wound healing.
- Mechanotransduction alterations in aged HDFs are not fully understood.
- Epigenetic mechanisms for rejuvenating aged cells present a challenge.
Purpose of the Study:
- Investigate the impact of compressive forces on aged HDFs.
- Explore epigenetic modifications and nuclear mechanotransduction.
- Identify pathways mediating compression-induced cellular rejuvenation.
Main Methods:
- Utilized a compressive force application model on aged HDFs.
- Assessed fibroblast activation via alpha-smooth muscle actin (ɑ-SMA).
- Analyzed epigenetic modifications (chromatin remodeling, histone methylation) and cellular migration.
- Conducted drug screening to identify signaling pathways.
- Evaluated collagen I levels in an aged skin model with implanted cell spheroids.
Main Results:
- Sustained compressive forces induced significant epigenetic modifications in aged HDFs.
- These epigenetic changes correlated with enhanced cellular migration and rejuvenation.
- The extracellular signal-regulated kinase (ERK) pathway was identified as a key mediator.
- Compressive forces on aged cell spheroids in an aged skin model increased collagen I levels.
Conclusions:
- Mechanical compression activates global epigenetic changes in aged fibroblasts.
- The ERK signaling pathway mediates compression-induced epigenetic rejuvenation.
- This approach holds potential for improving wound healing and skin regeneration.
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