1,25-dihydroxyvitamin D-3 prevents the conversion of adipose tissue into fibrous tissue in skin exposed to chronic UV irradiation

The hormonally active form of vitamin D (1,25(OH)(2)D-3), is known to be a physiological regulator of the proliferation and differentiation of skin ce lls including keratinocytes, fibroblasts, and adipocytes. In the present st udy, the efficacy of 1,25(OH),D, on the conversion of adipose tissue to fib rous tissue in photodamaged skin was investigated in a murine animal model. Groups of hairless mice were exposed to solar-simulating UV irradiation (l ambda max, 352 nm; UV distribution: 300-310 nm, 0.9%; 310-320 nm, 2.0%; 320 -420 nm, 97.1%) for 20 weeks at a dose of 10.8 J/m(2) five times weekly on weekdays. At the end of 20 weeks irradiation, wrinkling in the dorsal skin was induced. The histological and biochemical studies indicated that UV irr adiation caused a disappearance of adipocytes and concomitant accumulation of the extracellular matrix components (fibrosis), including collagen, hyal uronan, and chondroitin/dermatan, which are synthesized by fibroblasts. App lication of 1,25(OH)(2)D-3 an the dorsal skin prior to UV irradiation drama tically prevented both the disappearance of adipocytes and the accumulation of extracellular matrix components in the lower dermis, resulting in antiw rinkling. These findings indicate that 1,25(OH)(2)D-3 prevents the UV-induc ed abnormal differentiation and proliferation of adipocytes and fibroblasts , which arise from a common progenitor, mesenchymal cells. (C) 2001 Academi c Press