Microfibril-Associated Protein 5 Contributes to the Elastic Fiber Abnormalities in Aged Skin

Abstract

Elastic fibers, which contribute to the flexibility of tissues such as the skin, alveoli, and arteries, have a long half-life and are not regenerated once formed during the fetal stage. Consequently, the degradation of elastic fibers due to aging or inflammation can significantly impact tissue function. In the dermis, degeneration of elastic fibers is characterized by degradation in photoaging, driven by UV radiation, and structural abnormalities of elastic fibers in intrinsic aging. However, the mechanisms driving the abnormalities associated with intrinsic aging remain incomplete. This study aimed to identify the factors involved in the elastic fiber abnormalities associated with intrinsic aging of the dermis. Through a comprehensive analysis of gene expression, this study focused on microfibril-associated protein 5 (MFAP5) as a candidate gene responsible for the elastic fiber abnormalities associated with intrinsic aging. Immunofluorescence staining revealed that aged fibroblasts highly expressed MFAP5 and strongly localized it to aggregated elastic fibers. Furthermore, the elimination of MFAP5 expression suppressed elastic fiber aggregation. The exogenous addition of MFAP5 induced thickening and disorganization of elastic fibers, effects that were not observed with the overexpression of MFAP5 in young fibroblasts, which merely express MFAP5. Moreover, MFAP5 inhibited the interaction between latent transforming growth factor β binding protein 4 and fibulin-5, which are crucial for elastic fiber formation. These results suggest that excess MFAP5 expression associated with aging causes abnormalities in elastic fibers. Understanding the role of MFAP5 in elastic fiber abnormalities highlights its potential as a therapeutic target for mitigating intrinsic dermal aging and improving skin elasticity.