Vitamin A Antagonizes Decreased Cell Growth and Elevated Collagen-Degrading Matrix Metalloproteinases and Stimulates Collagen Accumulation in Naturally Aged Human Skin1

光老化 基质金属蛋白酶 结缔组织 人体皮肤 成纤维细胞 皮肤老化 化学 真皮成纤维细胞 内分泌学 细胞外基质 细胞生物学 胶原酶 体外 Ⅰ型胶原 羟脯氨酸 内科学 胶原蛋白,I型,α1 病理 生物 医学 生物化学 皮肤病科 遗传学
作者
James Varani,Roscoe L. Warner,Mehrnaz Gharaee‐Kermani,Sem H. Phan,Sewon Kang,Jin Ho Chung,Zeng Quan Wang,Subhash C. Datta,Gary J. Fisher,John J. Voorhees
出处
期刊:Journal of Investigative Dermatology [Elsevier]
卷期号:114 (3): 480-486 被引量:550
标识
DOI:10.1046/j.1523-1747.2000.00902.x
摘要

Damage to human skin due to ultraviolet light from the sun (photoaging) and damage occurring as a consequence of the passage of time (chronologic or natural aging) are considered to be distinct entities. Photoaging is caused in part by damage to skin connective tissue by increased elaboration of collagen-degrading matrix metalloproteinases, and by reduced collagen synthesis. As matrix metalloproteinase levels are known to rise in fibroblasts as a function of age, and as oxidant stress is believed to underlie changes associated with both photoaging and natural aging, we determined whether natural skin aging, like photoaging, gives rise to increased matrix metalloproteinases and reduced collagen synthesis. In addition, we determined whether topical vitamin A (retinol) could stimulate new collagen deposition in sun-protected aged skin, as it does in photoaged skin. Sun-protected skin samples were obtained from 72 individuals in four age groups: 18-29 y, 30-59 y, 60-79 y, and 80+ y. Histologic and cellular markers of connective tissue abnormalities were significantly elevated in the 60-79 y and 80+ y groups, compared with the two younger age groups. Increased matrix metalloproteinase levels and decreased collagen synthesis/expression were associated with this connective tissue damage. In a separate group of 53 individuals (80+ y of age), topical application of 1% vitamin A for 7 d increased fibroblast growth and collagen synthesis, and concomitantly reduced the levels of matrix-degrading matrix metalloproteinases. Our findings indicate that naturally aged, sun-protected skin and photoaged skin share important molecular features including connective tissue damage, elevated matrix metalloproteinase levels, and reduced collagen production. In addition, vitamin A treatment reduces matrix metalloproteinase expression and stimulates collagen synthesis in naturally aged, sun-protected skin, as it does in photoaged skin.
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