TY - JOUR
T1 - Betacellulin regulates hair follicle development and hair cycle induction and enhances angiogenesis in wounded skin
AU - Schneider, Marlon R.
AU - Antsiferova, Maria
AU - Feldmeyer, Laurence
AU - Dahlhoff, Maik
AU - Bugnon, Philippe
AU - Hasse, Sybille
AU - Paus, Ralf
AU - Wolf, Eckhard
AU - Werner, Sabine
N1 - Funding Information:
We thank Dr Ingrid Renner-Müller as well as Petra Renner and Tanja Mittmann for excellent animal care. This work was supported by grants from the German National Genome Research Network (to E.W.), the European Union (Grants WOUND and ULCERTHERAPY to S.W.), the Swiss National Science Foundation (Grant 3100A9-109340/1 to S.W. and MD–PhD Grant 3235B0-102873 to L.F.), and the DFG (Grant Pa 345/12-1 to R.P.).
PY - 2008/5
Y1 - 2008/5
N2 - Betacellulin (BTC) belongs to the EGF family, whose members play important roles in skin morphogenesis, homeostasis, and repair. However, the role of BTC in skin biology is still unknown. We employed transgenic mice overexpressing BTC ubiquitously to study its role in skin physiology. Immunohistochemistry revealed increased levels of BTC especially in the hair follicles and in the epidermis of transgenic animals. Expression of key markers of epithelial differentiation was unaltered, but keratinocyte proliferation was significantly increased. At post-natal day 1 (P1), transgenic mice displayed a significant retardation of hair follicle morphogenesis. At P17, when most follicles in control mice had initiated hair follicle cycling and had already entered into their first late catagen or telogen phase, all follicles of transgenic mice were still at the mid- to late catagen phases, indicating retarded initiation of hair follicle cycling. Healing of full-thickness excisional wounds and bursting strength of incisional wounds were similar in control and transgenic mice. However, an increase in the area covered by blood vessels at the wound site was detected in transgenic animals. These results provide evidence for a role of BTC in the regulation of epidermal homeostasis, hair follicle morphogenesis and cycling, and wound angiogenesis.
AB - Betacellulin (BTC) belongs to the EGF family, whose members play important roles in skin morphogenesis, homeostasis, and repair. However, the role of BTC in skin biology is still unknown. We employed transgenic mice overexpressing BTC ubiquitously to study its role in skin physiology. Immunohistochemistry revealed increased levels of BTC especially in the hair follicles and in the epidermis of transgenic animals. Expression of key markers of epithelial differentiation was unaltered, but keratinocyte proliferation was significantly increased. At post-natal day 1 (P1), transgenic mice displayed a significant retardation of hair follicle morphogenesis. At P17, when most follicles in control mice had initiated hair follicle cycling and had already entered into their first late catagen or telogen phase, all follicles of transgenic mice were still at the mid- to late catagen phases, indicating retarded initiation of hair follicle cycling. Healing of full-thickness excisional wounds and bursting strength of incisional wounds were similar in control and transgenic mice. However, an increase in the area covered by blood vessels at the wound site was detected in transgenic animals. These results provide evidence for a role of BTC in the regulation of epidermal homeostasis, hair follicle morphogenesis and cycling, and wound angiogenesis.
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U2 - 10.1038/sj.jid.5701135
DO - 10.1038/sj.jid.5701135
M3 - Article
C2 - 17960175
AN - SCOPUS:42149099334
VL - 128
SP - 1256
EP - 1265
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 5
ER -