Chemical peeling by SA-PEG remodels photo-damaged skin: suppressing p53 expression and normalizing keratinocyte differentiation.
Chemical peeling with salicylic acid in polyethylene glycol vehicle (SA-PEG), which specifically acts on the stratum corneum, suppresses the development of skin tumors in UVB-irradiated hairless mice. To elucidate the mechanism through which chemical peeling with SA-PEG suppresses skin tumor development, the effects of chemical peeling on photodamaged keratinocytes and cornified envelopes (CEs) were evaluated in vivo. Among UVB-irradiated hairless mice, the structural atypia and expression of p53 protein in keratinocytes induced by UVB irradiation were intensely suppressed in the SA-PEG-treated mice 28 days after the start of weekly SA-PEG treatments when compared to that in the control UVB-irradiated mice. Incomplete expression of filaggrin and loricrin in keratinocytes from the control mice was also improved in keratinocytes from the SA-PEG-treated mice. In photo-exposed human facial skin, immature CEs were replaced with mature CEs 4 weeks after treatment with SA-PEG. Restoration of photodamaged stratum corneum by treatment with SA-PEG, which may affect remodeling of the structural environment of the keratinocytes, involved the normalization of keratinocyte differentiation and suppression of skin tumor development. These results suggest that the stratum corneum plays a protective role against carcinogenesis, and provide a novel strategy for the prevention of photo-induced skin tumors.
Dainichi
Teruki
T
Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. dainichi@dermatol.med.kyushu-u.ac.jp
Amano
Satoshi
S
Matsunaga
Yukiko
Y
Iriyama
Shunsuke
S
Hirao
Tetsuji
T
Hariya
Takeshi
T
Hibino
Toshihiko
T
Katagiri
Chika
C
Takahashi
Motoji
M
Ueda
Setsuko
S
Furue
Masutaka
M
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D005260:Female; D000091344:Filaggrin Proteins; D006801:Humans; D007381:Intermediate Filament Proteins / Q000032:analysis; D015603:Keratinocytes / Q000737:chemistry / Q000187:drug effects* / Q000528:radiation effects; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D051379:Mice; D008812:Mice, Hairless; D009381:Neoplasms, Radiation-Induced / Q000517:prevention & control; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011837:Radiation-Protective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D012459:Salicylates / Q000494:pharmacology*; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects*; D015595:Skin Aging / Q000187:drug effects*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014466:Ultraviolet Rays
D016588:Anticarcinogenic Agents; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D008565:Membrane Proteins; D011837:Radiation-Protective Agents; D012459:Salicylates; D016159:Tumor Suppressor Protein p53; C064554:loricrin; D011092:Polyethylene Glycols