Extracellular Superoxide Dismutase Prevents Skin Aging by Promoting Collagen Production through the Activation of AMPK and Nrf2/HO-1 Cascades

[摘要] With aging, the skin becomes thin and drastically loses collagen. Extracellular superoxide dismutase (EC-SOD), also known as superoxide dismutase (SOD) 3, is the major SOD in the extracellular matrix of the tissues and is well-known to maintain the reduction.oxidation homeostasis and matrix components of such tissues. However, the role of EC-SOD in aging-associated reductions of skin thickness and collagen production is not wellstudied. In this study, we compared the histological differences in the dorsal skin of EC-SOD.overexpressing transgenic mice (Sod3thorn/thorn) of different age groups with that in wild-type mice and also determined the underlying signaling mechanism. Our data showed that the skin thickness in Sod3thorn/thorn mice significantly increased with aging compared with that in wild-type male mice. Furthermore, Sod3thorn/thorn mice had promoted collagen production through the activation of adenosine monophosphate-activated protein kinase and Nrf2/HO-1 pathways in aged mice. Interestingly, subcutaneous injection of adeno-associated virus.overexpressing ECSOD exhibited increased skin thickness and collagen expression. Furthermore, combined recombinant ECSOD and dihydrotestosterone treatment synergistically elevated collagen production through the activation of TGFb in human dermal fibroblasts. Altogether, these results showed that EC-SOD prevents skin aging by promoting collagen production in vivo and in vitro. Therefore, we propose that EC-SOD may be a potential therapeutic target for antiaging in the skin.

[发布日期] 2021-10-01