Connective tissue remodeling induced by carbon dioxide laser resurfacing of photodamaged human skin.
OBJECTIVE
To quantitatively examine the dynamics of molecular alterations involved in dermal remodeling after carbon dioxide (CO(2)) laser resurfacing of photodamaged human skin.


METHODS
Serial in vivo biochemical analyses after laser therapy.


METHODS
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.


METHODS
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.
Orringer
Jeffrey S
JS
Department of Dermatology, University of Michigan Medical School, Ann Arbor, USA. jorringe@umich.edu <jorringe@umich.edu>
Kang
Sewon
S
Johnson
Timothy M
TM
Karimipour
Darius J
DJ
Hamilton
Ted
T
Hammerberg
Craig
C
Voorhees
John J
JJ
Fisher
Gary J
GJ
D000368:Aged; D003238:Connective Tissue / Q000503:physiopathology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D062109:Dermatologic Surgical Procedures; D006801:Humans; D007150:Immunohistochemistry; D053685:Laser Therapy; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D011347:Procollagen / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015361:Rhytidoplasty; D012867:Skin / Q000378:metabolism; D015595:Skin Aging; D014945:Wound Healing
D016207:Cytokines; D011347:Procollagen; D012333:RNA, Messenger; D020782:Matrix Metalloproteinases