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Involvement of sonic hedgehog in cyclosporine A induced initiation of hair growth
J Dermatol Sci. 2007 Apr 26; [Epub ahead of print]
Cyclosporin A (CsA) is an immunosuppressant which can induce hypertrichosis as a side effect and attempts have been made to treat alopecia [1]. Studies using a mouse model suggested that CsA induces anagen [2], promotes hair growth [3] and suppresses catagen [4], but little is known about the mechanism involved. In androgenetic alopecia, increased telogen hairs are observed [5], so a beneficial effect of CsA, which induces anagen, would seem likely. Thus, the objective of this study was to elucidate the mechanism of anagen induction by CsA.
To measure changes in anagen induction by CsA, we developed a new method using mice as a model. Induction of anagen activity is usually measured by topically applying the chemicals to clipped telogen mice. However, with that method, it would be difficult to measure changes due to the stimulation of hair growth by clipping. For example, the degranulation of mast cells following clipping has been reported [6], and it is thought that gene expression in the skin during telogen is affected by stimulation with histamine released by degranulation. Therefore, we established a new method that could induce anagen by topical application of chemicals without clipping.
Shh is a protein in the hedgehog gene family, is secreted as a signal factor and is related to morphogenesis and organogenesis. Shh is expressed in the epithelial placode in mouse embryos and in hair follicles after birth [8]. From results with knockout mice, Shh appears to be essential as a regulatory factor during the morphogenesis of hair follicles [9]. Furthermore, Shh plays an important role in the shift to anagen because administration of a monoclonal antibody against Shh to mice shifting from telogen to anagen inhibits hair growth, while transfection of Shh to telogen mice using an adenovirus vector results in a shift from telogen to anagen hair follicles [10]. Thus, the increase in expression level of Shh observed following CsA treatment in this study, when considered with those other reports, suggests that Shh is related to the mechanism of anagen induction by CsA.
J Dermatol Sci. 2007 Apr 26; [Epub ahead of print]
Cyclosporin A (CsA) is an immunosuppressant which can induce hypertrichosis as a side effect and attempts have been made to treat alopecia [1]. Studies using a mouse model suggested that CsA induces anagen [2], promotes hair growth [3] and suppresses catagen [4], but little is known about the mechanism involved. In androgenetic alopecia, increased telogen hairs are observed [5], so a beneficial effect of CsA, which induces anagen, would seem likely. Thus, the objective of this study was to elucidate the mechanism of anagen induction by CsA.
To measure changes in anagen induction by CsA, we developed a new method using mice as a model. Induction of anagen activity is usually measured by topically applying the chemicals to clipped telogen mice. However, with that method, it would be difficult to measure changes due to the stimulation of hair growth by clipping. For example, the degranulation of mast cells following clipping has been reported [6], and it is thought that gene expression in the skin during telogen is affected by stimulation with histamine released by degranulation. Therefore, we established a new method that could induce anagen by topical application of chemicals without clipping.
Shh is a protein in the hedgehog gene family, is secreted as a signal factor and is related to morphogenesis and organogenesis. Shh is expressed in the epithelial placode in mouse embryos and in hair follicles after birth [8]. From results with knockout mice, Shh appears to be essential as a regulatory factor during the morphogenesis of hair follicles [9]. Furthermore, Shh plays an important role in the shift to anagen because administration of a monoclonal antibody against Shh to mice shifting from telogen to anagen inhibits hair growth, while transfection of Shh to telogen mice using an adenovirus vector results in a shift from telogen to anagen hair follicles [10]. Thus, the increase in expression level of Shh observed following CsA treatment in this study, when considered with those other reports, suggests that Shh is related to the mechanism of anagen induction by CsA.
