Possible Involvement of Basement Membrane Damage in Skin Photoaging

摘要

Aging of sun-exposed skin is accelerated by three major environmental factors: UV radiation, dryness, and oxidation. UV radiation exposure is the most influential factor in skin aging (so-called photoaging). To find ways to protect against damage caused by UV exposure and to delay photoaging, we studied internal changes of sun-exposed skin compared with those of sun-protected skin. We found that the basement membrane (BM) at the dermal–epidermal junction (DEJ) of sun-exposed skin becomes damaged and multilayered and partly disrupted compared with that of sun-protected skin. BM plays important roles in maintaining a healthy epidermis and dermis, and repeated damage destabilizes the skin, accelerating the aging process. Matrix metalloproteinases (MMPs) and urinary plasminogen activator are increased in UV-irradiated skin. MMPs are detected in the cornified layer in sun-exposed skin, but not in sun-protected skin. Using skin-equivalent models, we found that MMPs and plasmin cause BM damage and that the reconstruction of BM is enhanced by inhibiting these proteinases, as well as by increasing the synthesis of BM components. Enhancement of BM repair mechanisms may be a useful strategy in retarding photoaging.Abbreviations: BM, basement membrane; DEJ, dermal–epidermal junction; MMP, matrix metalloproteinase; PA, plasminogen activator; TIMP, tissue inhibitors of metalloproteinases; tPA, tissue-type plasminogen activator; uPA, urokinase-type plasminogen activator