Elastin microfibril interface-located protein 1 and its catabolic enzyme, cathepsin K, regulate the age-related structure of elastic fibers in the skin.

The elastic fiber structure becomes shorter, thicker, and curved with age. Nonetheless, the proteins and catabolic enzymes influencing the maintenance of and change in the three-dimensional (3D) structure of elastic fibers remain unknown. This study aimed to identify the proteins involved in the maintenance and degeneration of elastic fiber structures. We performed a combined 3D structural analysis using tissue decolorization technology and mRNA abundance and comprehensive protein expression of tissue-derived cells. The relationship between the proteins was evaluated. Elastin microfibril interface-located protein 1 (EMILIN-1) and cathepsin K (CTSK) were implicated in structural changes in elastic fibers with aging. EMILIN-1 and CTSK levels were highly correlated and changed with age. CTSK was identified as the degrading enzyme of EMILIN-1. CTSK fragmented the otherwise linearly existing dermal elastic fiber structure, with more evident changes in oxytalan fibers. EMILIN-1 expression in fibroblasts was increased by co-culturing with keratinocytes. Furthermore, CTSK expression was increased by UV stress in keratinocytes, resulting in decreased EMILIN-1 expression. Using our new assessment strategy, we observed that EMILIN-1 and CTSK are highly linked to changes in the elastic fiber structure with aging. These results indicate that suppressing CTSK expression and increasing EMILIN-1 expression might be an effective approach to prevent elastic fiber morphological changes that lead to wrinkles and sagging. Furthermore, EMILIN-1 in the dermis increases due to interaction with the epidermis, which could provide a new target for the therapeutic care of elastic fibers (including preservation of oxytalan fibers) in epidermis-dermis interaction. © 2022 Wiley Periodicals LLC.

Citation

Shinya Kondo, Takeshi Tohgasaki, Soichiro Shiga, Shino Nishizawa, Shioji Ishiwatari, Shinsuke Ishikawa, Akira Takeda, Tetsuhito Sakurai. Elastin microfibril interface-located protein 1 and its catabolic enzyme, cathepsin K, regulate the age-related structure of elastic fibers in the skin. Journal of cosmetic dermatology. 2022 Jan 21

PMID: 35064622

search → result