Extracellular Matrix Nitration: Role in Elastic Fiber Accumulation and Skin Photoaging

Prolonged ultraviolet (UV) exposure causes skin photoaging with clinical features of wrinkles, loss of elasticity, and roughness. Histologically, photoaging is characterized by the accumulation of abnormally disorganized elastic fibers in the upper dermis, and various post-translational modifications are assumed to be associated with this process. Protein tyrosine nitration, which is mediated by reactive nitrogen species formed by nitric oxide and superoxide, is one of the post-translational modifications that has increasingly been recognized as a functionally significant protein modification. This study aimed to investigate the involvement of protein nitration in abnormal elastin accumulation and skin photoaging. Immunohistochemical staining of skin sections from elderly women revealed that abnormally accumulated elastin in the photoaged dermis (cheek) was more strongly colocalized with nitrotyrosine than elastin in the chronologically aged dermis (buttock). Moreover, an immunoprecipitation assay showed that dermal fibroblasts exposed to UV-A induced tyrosine nitration of elastin. Experimental nitration of elastin fibers altered the physical properties of elastin, with the formation of large multimeric assemblies of human recombinant tropoelastin and curled and aggregated bundles of elastin fibers, resulting in enhanced stiffness and decreased elasticity of elastin. In addition, nitrated elastin showed resistance to degradation by elastase secreted by neutrophils and fibroblasts. Furthermore, the nitrotyrosine-reducing agent, clove extract, inhibited peroxynitrite-induced elastin aggregation and improved human skin elasticity. These results suggest that elastin nitration caused by UV exposure leads to abnormal elastin accumulation, which alters the mechanical properties of the skin and results in the progression of photoaging. Therefore, this study proposes nitration as a potential novel target for preventing skin photoaging.