Skin presenting a higher level of caspase-14 is better protected from UVB irradiation according to in vitro and in vivo studies.
Caspase-14, a cysteine endoproteinase belonging to the conserved family of aspartate-specific proteinases, was shown to play an important role in the terminal differentiation of keratinocytes and barrier function of the skin. In the present study, we developed a biofunctional compound that we described as a modulator of caspase-14 expression. Using normal human keratinocytes (NHK) in culture and human skin biopsies, this compound was shown to increase caspase-14 expression and partially reverse the effect of caspase-14-specific siRNA on NHK. Moreover, the increase in filaggrin expression visualized on skin biopsies and the recovery of the barrier structure after tape-stripping indicated that this compound could exhibit a beneficial effect on the skin barrier function. Considering the possible link between caspase-14 and the barrier function, a UVB irradiation on NHK and skin biopsies previously treated with the caspase-14 inducer, was performed. Results indicated that pretreated skin biopsies exhibited less signs of UV damage such as active caspase-3 and cyclobutane pyrimidine dimers (CPDs). Likewise, pretreated NHK were protected from UV-induced genomic DNA damage, as revealed by the Comet Assay. Finally, a clinical test showed a reduction of transepidermal water loss (TEWL) on the treated skin compared with placebo, under UV stress condition, confirming a protecting effect. Taken together, these results strongly suggest that, by increasing caspase-14 expression, the biofunctional compound could exhibit a protective effect on the skin barrier function, especially in case of barrier damage and UV irradiation.
ISP Vincience, ISP Global Skin Research Center, Sophia Antipolis, France.
Laurine
L
Bergeron
Catherine
C
Gondran
Gilles
G
Oberto
Noelle
N
Garcia
Jean Marie
JM
Botto
Karine
K
Cucumel
Claude
C
Dal Farra
Nouha
N
Domloge
D000328:Adult; D001706:Biopsy; D053456:Caspase 14 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D004249:DNA Damage / Q000187:drug effects / Q000528:radiation effects; D005260:Female; D000091344:Filaggrin Proteins; D015870:Gene Expression; D006801:Humans; D007381:Intermediate Filament Proteins / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects / Q000201:enzymology* / Q000528:radiation effects; D008875:Middle Aged; D011740:Pyrimidine Dimers / Q000378:metabolism; D034741:RNA, Small Interfering; D011832:Radiation Injuries / Q000517:prevention & control; D012867:Skin / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology* / Q000528:radiation effects; D012879:Skin Physiological Phenomena / Q000187:drug effects / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects*; D014870:Water Loss, Insensible / Q000187:drug effects; D055815:Young Adult
C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D011740:Pyrimidine Dimers; D034741:RNA, Small Interfering; D053456:Caspase 14; D053148:Caspase 3