Ergocalciferol promotes in vivo differentiation of keratinocytes and reduces photodamage caused by ultraviolet irradiation in hairless mice.
BACKGROUND
Ergocalciferol (VD(2)) is usually administered orally and it is metabolized to produce its biologically active metabolites in the liver and kidney. Active vitamin D is a well-known potent regulator of cell growth and differentiation.


OBJECTIVE
Active vitamin D such as 1,25-dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)) prevents photodamage, including wrinkles and morphologic alterations. However, its clinical and cosmetic use is limited because of its potent, associated effect on calcium metabolism. We examined the efficacy of vitamin D analogues with few adverse effects for preventing skin photodamage.


METHODS
Topical application of VD(2) to hairless mouse dorsal skin, and exposure to solar-simulating ultraviolet (UV) radiation at a dose of 10.8 J/cm(2) (UVA) were performed for 15 weeks, five times a week on weekdays. At the end of the final irradiation, histological and analytical studies were performed.


RESULTS
Topical application of VD(2) significantly prevented wrinkle formation and abnormal accumulation of extracellular matrix components. In addition, VD(2) suppressed excessive secretion of IL-6 induced by UV irradiation in cultured human normal keratinocytes, in a dose-dependent manner.


CONCLUSIONS
VD(2) promoted keratinocytes differentiation in the epidermis and showed diverse physiological effects, the same as the active form of VD(3). The results suggested that the suppression of skin photodamage involved the promotion of keratinocytes differentiation and suppression of IL-6 secretion induced by exposure to UV. Topical application of VD(2) may become an effective means to suppress solar UV-induced human skin damage.
Mitani
Hiroaki
H
Kose Co. Research & Development Division, 1-18-4 Azusawa, Itabashi-ku, Tokyo, Japan. h-mitani@kose.co.jp
Naru
Eiji
E
Yamashita
Mika
M
Arakane
Kumi
K
Suzuki
Tadashi
T
Imanari
Toshio
T
D000279:Administration, Cutaneous; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000187:drug effects / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D004872:Ergocalciferols / Q000008:administration & dosage / Q000627:therapeutic use*; D005109:Extracellular Matrix / Q000187:drug effects / Q000528:radiation effects; D005260:Female; D006025:Glycosaminoglycans / Q000032:analysis / Q000528:radiation effects; D006801:Humans; D015850:Interleukin-6 / Q000032:analysis / Q000528:radiation effects; D015603:Keratinocytes / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects; D051379:Mice; D008812:Mice, Hairless; D010787:Photosensitivity Disorders / Q000517:prevention & control*; D011829:Radiation Dosage; D012867:Skin / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects; D015595:Skin Aging / Q000187:drug effects / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects*
D004872:Ergocalciferols; D006025:Glycosaminoglycans; D015850:Interleukin-6; D003094:Collagen