Ultraviolet B induces hyperproliferation and modification of epidermal differentiation in normal human skin grafted on to nude mice.
BACKGROUND
For ethical and technical reasons, the in vivo biological effects of ultraviolet (UV) radiation on skin are difficult to study in human volunteers. The use of human skin grafted on to nude mice may circumvent this difficulty.


OBJECTIVE
To investigate the effects of a single moderate UVB exposure on human skin grafted on to nude mice.


METHODS
Modifications of epidermal differentiation markers and patterns of keratin expression were assessed from 24 h to 14 days after a physiological UVB irradiation characterized by the induction of sunburn cells.


RESULTS
During the first 48 h postexposure, involucrin, loricrin, transglutaminase type I, filaggrin and keratin K2e expression were altered together with the formation of abnormal horny layers. Constitutive keratin K14 was increased while keratin K10 expression was delayed. Newly synthesized keratins K6, K16, K17 and K19 were induced in parallel with an increase in the epidermal proliferation rate. A progressive normalization of both keratinocyte proliferation and differentiation took place during the following days, reaching completion within 2 weeks.


CONCLUSIONS
Exposure of human skin to a UVB dose corresponding to a mild sunburn reaction induces epidermal hyperproliferation and alterations of several constitutive differentiation markers, as well as a drastic modification in the pattern of epidermal keratins. Although these modifications were shown to be progressively reversed in a single exposure model, the data also suggest that subsequent UV exposures occurring during the recovery period may lead to potentially deleterious long-term consequences, such as photoageing and photocarcinogenesis. Grafted human skin appeared to be an attractive and promising model for investigating the biological consequences of UVB radiation in vivo.
Del Bino
S
S
L'Oréal Research, Clichy, France, and Galderma R&D, 635 route des Lucioles, BP87, 06902 Sophia Antipolis, France. sdelbino@recherche.loreal.com
Vioux
C
C
Rossio-Pasquier
P
P
Jomard
A
A
Demarchez
M
M
Asselineau
D
D
Bernerd
F
F
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002454:Cell Differentiation / Q000528:radiation effects*; D002455:Cell Division / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D000091344:Filaggrin Proteins; D006801:Humans; D007381:Intermediate Filament Proteins / Q000032:analysis; D015603:Keratinocytes / Q000502:physiology / Q000528:radiation effects*; D007633:Keratins / Q000032:analysis; D008565:Membrane Proteins / Q000032:analysis; D051379:Mice; D008819:Mice, Nude; D011498:Protein Precursors / Q000032:analysis; D011832:Radiation Injuries / Q000503:physiopathology; D012867:Skin / Q000528:radiation effects*; D016038:Skin Transplantation; D013471:Sunburn / Q000503:physiopathology; D011503:Transglutaminases / Q000032:analysis; D014183:Transplantation, Heterologous; D014466:Ultraviolet Rays / Q000009:adverse effects*
D015415:Biomarkers; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D008565:Membrane Proteins; D011498:Protein Precursors; C064554:loricrin; C032253:involucrin; D007633:Keratins; D011503:Transglutaminases; C105804:transglutaminase 1