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Published on: October 25, 2018
Connective tissue remodeling induced by carbon dioxide laser resurfacing of photodamaged human skin
Jeffrey S Orringer1, Sewon Kang, Timothy M Johnson
1Department of Dermatology, University of Michigan Medical School, Ann Arbor, USA. jorringe@umich.edu <jorringe@umich.edu>
Objective:
To quantitatively examine the dynamics of molecular alterations involved in dermal remodeling after carbon dioxide (CO(2)) laser resurfacing of photodamaged human skin.
Design:
Serial in vivo biochemical analyses after laser therapy.
Setting:
Academic referral center, Department of Dermatology, University of Michigan, Ann Arbor. Subjects Volunteer sample of 28 adults, 48 to 76 years old, with clinically evident photodamage of the forearms. Intervention Focal CO(2) laser resurfacing of photodamaged forearms and serial biopsies at baseline and various times after treatment.
Main Outcome Measures:
Reverse transcriptase real-time polymerase chain reaction technology and immunohistochemistry were used to assess levels of type I and type III procollagens; matrix metalloproteinases (MMPs) 1, 3, 9, and 13; tropoelastin; fibrillin; primary cytokines interleukin 1beta and tumor necrosis factor alpha; and profibrotic cytokine transforming growth factor beta1.
Results:
Production of type I procollagen and type III procollagen messenger RNA peaked at 7.5 and 8.9 times baseline levels, respectively, 21 days after treatment and remained elevated for at least 6 months. Increases in messenger RNA levels of several cytokines (interleukin 1beta, tumor necrosis factor alpha, and transforming growth factor beta1) preceded and/or accompanied changes in collagen levels. Marked increases in messenger RNA levels of MMP-1 (39 130-fold), MMP-3 (1041-fold), MMP-9 (75-fold), and MMP-13 (767-fold) were noted. Levels of fibrillin and tropoelastin rose in a delayed fashion several weeks after treatment.
Conclusions:
The biochemical changes seen after CO(2) laser resurfacing proceed through a well-organized and highly reproducible wound healing response that results in marked alterations in dermal structure. These quantitative changes may serve as a means for comparison as other therapeutic modalities meant to improve the appearance of photodamaged skin are evaluated.
Insights
Carbon dioxide (CO(2)) laser resurfacing significantly boosts collagen production and matrix metalloproteinases (MMPs) in photodamaged skin, initiating a reproducible wound healing response for dermal remodeling.
Area of Science:
- Dermatology
- Molecular Biology
- Biochemistry
Background:
- Photodamaged skin exhibits altered dermal structure and molecular composition.
- Carbon dioxide (CO(2)) laser resurfacing is a common treatment for skin aging and photodamage.
Purpose of the Study:
- To quantitatively analyze the molecular changes in dermal remodeling following CO(2) laser resurfacing of photodamaged human skin.
- To understand the temporal dynamics of key molecular mediators involved in the healing process.
Main Methods:
- Serial in vivo biochemical analyses were performed on skin biopsies from 28 adult subjects with photodamaged forearms.
- Reverse transcriptase real-time polymerase chain reaction and immunohistochemistry were used to quantify procollagens, MMPs, tropoelastin, fibrillin, and cytokines.
Main Results:
- Type I and III procollagen mRNA levels increased significantly, peaking at 21 days post-treatment and remaining elevated for at least 6 months.
- Expression of pro-inflammatory cytokines (IL-1β, TNF-α) and transforming growth factor-β1 increased, preceding or coinciding with collagen changes.
- Matrix metalloproteinase (MMP) mRNA levels, particularly MMP-1, MMP-3, and MMP-13, showed dramatic increases (up to 130-fold).
- Fibrillin and tropoelastin levels demonstrated a delayed increase several weeks after treatment.
Conclusions:
- CO(2) laser resurfacing induces a highly organized and reproducible wound healing cascade, leading to significant dermal remodeling.
- The quantitative molecular data provide a benchmark for evaluating other treatments aimed at improving photodamaged skin.
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