PHOTOCHEMISTRY AND PHOTOBIOLOGY OF MATRIX COLLAGENS

基质胶原的光化学和光生物学

• 批准号: 6204195
• 负责人: JULIAN M MENTER
• 金额: $ 9.59万
• 依托单位: MOREHOUSE SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至 2000-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6204195
• 关键词: aging; collagen; collagenase; enzyme activity; enzyme induction /repression; extracellular matrix; fibroblasts; gas chromatography mass spectrometry; hairless mouse; high performance liquid chromatography; laboratory mouse; laboratory rabbit; matrigel; photoactivation; photobiology; photochemistry; photostimulus; protein sequence; protein structure function; radiation carcinogenesis; skin disorder; skin neoplasms; solar radiation; sunburn; ultraviolet radiation; wound healing

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.

阳光照射与表皮（前）恶性肿瘤明确相关 以及皮肤的“光老化”。紫外线与 细胞外基质胶原可能起重要作用。体内真皮 胶原蛋白损伤是由紫外线诱导的胶原酶刺激引起的 皮肤成纤维细胞中的活性，这可能部分是由于 光转化的（“外来”）胶原蛋白。同样，光转化 血管和/或基底胶原的沉积可能提供不利的环境， 内皮细胞（EC）的生长和活力，导致改变 细胞骨架形态，否则有助于观察到的总 紫外线对这些组件造成的损害。为了解决这个问题，我们 建议研究各种波长对结构的影响， 真皮和基质胶原蛋白以及重建基底的功能 （MATRIGEL）膜，并确定这些光转换是否 可引起胶原酶产生和/或EC变化。我们将（1）辐射 纯化的胶原蛋白与各种波长的紫外线。我们将监测变化 在结构、比浊法、氨基酸谱、对 胶原酶、荧光特性。(2)孵育真皮成纤维细胞， EC与（光转化）胶原蛋白。在（未）辐照基质上生长EC 基质或与III型或IV型胶原孵育。成纤维细胞将 在正常小鼠上检测存活力、生长和胶原酶诱导。 和UV变换矩阵。将对Ec进行生存能力，生长， 流动性和细胞骨架形态学变化。(3)评估保护性 标准防晒制剂对体外胶原蛋白的作用 受到太阳波长的伤害。这些研究的结果应该能让我们 在光致癌、光老化和创伤中起重要作用 可用于美容、防晒等 行业