The extracellular matrix (ECM) has important functions in the maintenance of proper skin tensile strength and elasticity. ECM components are found in the dermis, in which mesenchyme-derived fibroblasts produce most of the ECM components, including several types of collagen molecules, polymeric glycosaminoglycans, and elastic fibers. Of these, type 1 collagen is the most abundant structural protein in skin connective tissue and has a direct influence on skin tension. During the aging process, skin gradually loses mechanical strength and elasticity, which leads to the formation of wrinkles. This phenomenon is largely due to the collapse of dermal connective tissue, which coincides with the loss of fibroblast proliferation and reduced ECM production. An abnormality in type I collagen synthesis has been suggested to cause an imbalance in ECM metabolism and the clinical changes observed in aged skin. Therefore, it has long been believed that enhancing fibroblast activity, in the context of ECM production, may help maintain skin texture.
As the intracellular signaling cascades p42/44 ERK and p38 MAPK are implicated in the regulation of ECM production-, we investigated the effect of cedrol on MAPK activation. As shown in , cedrol treatment led to quick phosphorylation of p42/44 ERK and p38 MAPK. Additionally, the phosphorylation level of Akt, an important signaling molecule for cell survival, also increased following treatment with cedrol. As the Smad pathway is critical for collagen synthesis during the wound healing process-, we also investigated Smad protein activation. However, cedrol did not influence the Smad2/3phosphorylation, suggesting that cedrol affects ECM production via the intracellular MAPK signaling cascades.
A number of intracellular signal transduction pathways have been reported to play a role in the regulation of many cellular functions. For example, cell growth, differentiation, and apoptosis are all tightly regulated by the activation status of many intracellular signaling systems-. Gene expression is also regulated by an intracellular signaling system. Intracellular signaling cascades including MAPK, Akt, and Smad, are involved in the regulating collagen expression. The primary role of MAPK has been previously recognized as procollagen synthesis,,. We have demonstrated that cedrol significantly increases the phosphorylation of ERK1/2, p38 MAPK and Akt. Cedrol apparently acts as an intracellular signal modulator based on the association between collagen synthesis and MAPK activation. As cedrol has a two ring-structure and shows oily characteristics, cedrol probably penetrates the plasma membrane and directly affects intracellular signaling. However, the precise intracellular action mechanism of cedrol remains to be determined.