PHOTOCHEMISTRY AND PHOTOBIOLOGY OF MATRIX COLLAGENS

阳光照射与表皮（前）恶性肿瘤明确相关

Sun exposure is unequivocally associated with epidermal (pre)malignancies and with dermal "photo-aging". The direct interaction between UV and extracellular matrix collagens may play an important role. In vivo dermal collagen damage results from UV-induced stimulation of collagenase activity in dermal fibroblasts, which could arise partly as a consequence of photo-transformed ("foreign") collagen. Similarly, photo-transformation of vascular and/or basement collagens may provide a milieu unfavorable for endothelial cell (EC) growth and viability, result in altered cytoskeletal morphology, and otherwise contribute to the total observed UV-induced damage to these components. To address this hypothesis, we propose to study the effect of various wavelengths on the structure and function of dermal and matrix collagens as well as reconstituted basement (MATRIGEL) membranes and to ascertain whether these photo-transformations may elicit collagenase production and/or EC changes. We will (1) Irradiate purified collagens with various wavelengths of UV. We will monitor changes in structure, turbidimetry, amino acid profile, susceptibility to collagenase, fluorescence properties. (2) Incubate dermal fibroblasts and EC with (photo-transformed) collagens. Grow EC on (un)irradiated MATRIGEL matrix or incubate them with types III or IV collagens. Fibroblasts will be tested for viability, growth, and for collagenase induction on normal and UV-transformed matrices. Ec will be tested for viability, growth, mobility, and cytoskeletal morphology changes. (3) Assess the protective effect for standard sunscreen preparations against in vitro collagen damage by solar wavelength. Results from these studies should shed insight into processes important in photo-carcinogenesis, photo-aging and wound healing, and could be applicable to the cosmetic and photo-protection industries.