Role of collagen degradation pathway in sphingomyelin synthase 2-deficient mouse skin

Abstract

Sphingomyelin synthase (SMS) is the only enzyme that synthesizes sphingomyelin from ceramide. The role of sphingomyelin synthase in epidermis is being understood, but there is no report on its role in the dermis. Quantitative and qualitative evaluation of collagen in SMS2-deficient mice reveals the role of SMS2 in collagen production. SMS2-deficient mice were used for in this study. The dermis thickness was measured by Elastica van Gieson staining, the collagen fiber was observed by Scanning Electron Microscopy, the collagen content by ELISA, the ceramide and sphingomyelin content by Thin Layer Chromatography, the collagen-generating and metabolizing gene expression level by RT-PCR, and MMP13 protein level was measured by western blotting. Thinner dermis in these mice compared to wild-type mice. A reduced number of collagen fibers were observed, and decreased levels of type I collagen and sphingolipids. Gene expression levels of collagen production-related genes in the dermis were found to be unaltered. The expression of several genes related to collagen degradation was found to be affected. The expression level of TNFα and MMP13 and MMP13 protein levels were increased relative to those of wild-type mice, while the expression level of TIMP1 was decreased. These results indicate that SMS is involved not only in maintaining the sphingolipid content of the epidermal barrier but also in maintaining collagen homeostasis. Further elucidation of the role of SMS2 in the skin may lead to SMS2 comprising a new target for the treatment of skin diseases and the development of functional cosmetics.