Abstract
In most mammals, each hair follicle undergoes a cyclic process of growing, regressing and resting phases (anagen, catagen, telogen, respectively) called the hair cycle. Various biological factors have been reported to regulate or to synchronize with the hair cycle. Some factors involved in the extracellular matrix, which is a major component of skin tissue, are also thought to regulate the hair cycle. We have focused on an enzyme that degrades elastin, which is associated with skin elasticity. Since our previous study identified skin fibroblast elastase as neprilysin (NEP), we examined the fluctuation of NEP enzyme activity and its expression during the synchronized hair cycle of rats. NEP activity in the skin was elevated at early anagen, and decreased during catagen to telogen. The expression of NEP mRNA and protein levels was modulated similarly. Immunostaining showed changes in NEP localization throughout the hair cycle, from the follicular epithelium during early anagen to the dermal papilla during catagen. To determine whether NEP plays an important role in regulating the hair cycle, we used a specific inhibitor of NEP (NPLT). NPLT was applied topically daily to the dorsal skin of C3H mice, which had been depilated in advance. Mice treated with NPLT had significantly suppressed hair growth. These data suggest that NEP plays an important role in regulating the hair cycle by its increased expression and activity in the follicular epithelium during early anagen.
Highlights
As the hair cycle is one of the intrinsic and cyclic systems of regenerating tissue, the mechanism of its regulation is intriguing with respect to tissue reconstruction
To determine whether extracellular matrix (ECM)-degrading enzymes fluctuate with the hair cycle in skin including the hair follicle, we measured the activities of Type I and Type IV collagenases and elastase as typical ECM-degrading enzymes
The hair cycle is a process of cyclic tissue remodeling, and it considered as a complex process that involves many factors, for example, growth factors, cytokines, hormones, adhesion molecules [39] and related enzymes
Summary
As the hair cycle is one of the intrinsic and cyclic systems of regenerating tissue, the mechanism of its regulation is intriguing with respect to tissue reconstruction. There are many biological factors which have been reported to regulate or to synchronize with the hair cycle. Those factors can be divided into several classifications, such as hormones, growth factors, enzymes and transcription factors. With regard to the ECM, proteoglycans have been well investigated and associated with the hair cycle [11,12,13,14,15]. Only a few matrix degrading enzymes have been reported to be associated with the hair cycle so far, such as type IV collagenase [16], matrix metalloproteinase (MMP)-2 and TIMP-1 [1,17]. Since we previously identified neprilysin (NEP) as dermal fibroblast elastase [18], we focused on the potential role of NEP in the regulation of the hair cycle
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