Acute or chronic topical retinoic acid treatment of human skin in vivo alters the expression of epidermal transglutaminase, loricrin, involucrin, filaggrin, and keratins 6 and 13 but not keratins 1, 10, and 14.
Histologic and immunocytochemical analyses were performed on cutaneous biopsies from 10 patients treated with retinoic acid under occlusion for 4 d compared to biopsies from 19 patients treated nightly for 16 weeks. Acute application of RA caused epidermal thickening (9 of 10 samples), stratum granulosum thickening (7 of 10), parakeratosis (4 of 10), a marked increase in the number of cell layers expressing epidermal transglutaminase (7 of 10), and focal expression of two non-epidermal keratins, K6 (8 of 10) and K13 (2 of 10), changes also observed with chronic treatment. Involucrin, filaggrin, and loricrin were also altered in samples from both acute and chronic treatment. An increased number of cell layers expressed both involucrin and filaggrin from both the acute (7 of 10) and chronic (14 of 19) treatment groups. In the acute group, loricrin expression was significantly reduced or absent in some regions of the epidermis (5 of 10), whereas most chronic samples showed an increased number of cell layers expressing loricrin (12 of 19). The pattern of expression of three major epidermal differentiation products, keratins K1, K10, and K14, was not significantly altered in any of the acute or chronic samples, although there was a slight reduction in the detection of K10 in two of the acute samples. Thus, acute topical RA treatment under occlusion caused substantial changes in the epidermis, and reproduced most, but not all of the effects of chronic treatment.
Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland.
D S
DS
Rosenthal
C E
CE
Griffiths
S H
SH
Yuspa
D R
DR
Roop
J J
JJ
Voorhees
D000287:Administration, Topical; D000091344:Filaggrin Proteins; D006801:Humans; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000032:analysis*; D007633:Keratins / Q000032:analysis* / Q000235:genetics; D008565:Membrane Proteins / Q000032:analysis*; D011498:Protein Precursors / Q000032:analysis*; D012333:RNA, Messenger / Q000032:analysis; D012867:Skin / Q000737:chemistry / Q000187:drug effects*; D011503:Transglutaminases / Q000032:analysis*; D014212:Tretinoin / Q000008:administration & dosage / Q000494:pharmacology*
C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D008565:Membrane Proteins; D011498:Protein Precursors; D012333:RNA, Messenger; C064554:loricrin; D014212:Tretinoin; C032253:involucrin; D007633:Keratins; D011503:Transglutaminases