Chemical Peeling by SA-PEG Remodels Photo-damaged Skin: Suppressing p53 Expression and Normalizing Keratinocyte Differentiation  Teruki Dainichi, Satoshi Amano, Yukiko Matsunaga, Shunsuke Iriyama, Tetsuji Hirao, Takeshi Hariya, Toshihiko Hibino, Chika Katagiri, Motoji Takahashi, Setsuko Ueda, Masutaka Furue  Journal of Investigative Dermatology  Volume 126, Issue 2, Pages 416-421 (February 2006) DOI: 10.1038/sj.jid.5700066 Copyright © 2006 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Histology of skin from mice that underwent UVB irradiation followed by weekly treatments with SA-PEG chemical peeling. SA-PEG chemical peeling was performed on day 0, day 7, day 14, and day 21. The stratum corneum recovered its normal thickness until 3 days after the treatment of chemical peeling. (a–d) In HE strain. D3: (a) control and (b) SA-PEG. D28: (c) control and (d) SA-PEG. (e–h) Expression of p53 protein in skin specimens from mice that underwent UVB irradiation followed by weekly treatments with SA-PEG chemical peeling. D3: (e) control and (f) SA-PEG. D28: (g) control and (h) SA-PEG. (i) Histology of no-UVB, no-peel skin in HE stain. (j–l) Quantitative evaluation of epidermal thickness and p53 expression in skin specimens from mice that underwent UVB irradiation followed by weekly treatments with SA-PEG chemical peeling. SA-PEG chemical peeling was performed on day 0, day 7, day 14, and day 21. (j) Epidermal thickness. (k) Percentage of p53-positive nonbasal cells: the ratio of the number of p53-positive nonbasal cells to the number of all p53-positive cells. (l) p53-positive basal cells/mm. Number of p53-positive basal cells per mm of basement membrane other than adnexal epithelia. NT, no treatment with SA-PEG; SA, SA-PEG. Journal of Investigative Dermatology 2006 126, 416-421DOI: (10.1038/sj.jid.5700066) Copyright © 2006 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Expression of filaggrin and loricrin in the skin specimens from mice that underwent UVB irradiation followed by weekly treatments with SA-PEG chemical peeling. SA-PEG chemical peeling was performed on day 0, day 7, day 14, and day 21. Filaggrin, day 3: (a) control and (b) SA-PEG; day 28: (c) control and (d) SA-PEG. Loricrin, day 3: (e) control and (f) SA-PEG; day 28: (g) control and (h) SA-PEG. Journal of Investigative Dermatology 2006 126, 416-421DOI: (10.1038/sj.jid.5700066) Copyright © 2006 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 3 Detection of mature and immature CEs in the stratum corneum from human volunteers. Before and after chemical peeling with SA-PEG, CEs in the tape-stripped stratum corneum from the face of volunteers were subjected to double staining with Nile red and fluorescein isothiocyanate-labeled anti-involucrin. Mature CEs are stained by Nile red and immature CEs are stained by anti-involucrin (green). (a) A CE from case 1 before SA-PEG treatment. (b) A CE from case 1 obtained 4 weeks after the SA-PEG treatment. (c) A CE from case 2 before SA-PEG treatment. (d) A CE from case 2 obtained 4 weeks after the SA-PEG treatment. (e) Time course of the maturation of CEs from the skin of volunteers (n=14) treated with SA-PEG. The average percentage of immature CEs to the total number of CEs is plotted. Journal of Investigative Dermatology 2006 126, 416-421DOI: (10.1038/sj.jid.5700066) Copyright © 2006 The Society for Investigative Dermatology, Inc Terms and Conditions