1. Activating Hair Follicle Stem Cells via R-spondin2 to Stimulate Hair Growth.
- Author
-
Smith AA, Li J, Liu B, Hunter D, Pyles M, Gillette M, Dhamdhere GR, Abo A, Oro A, and Helms JA
- Subjects
- Aged, Animals, Cell Membrane metabolism, Cell Proliferation, Cell Survival, Genes, Reporter, Hair Follicle transplantation, Humans, Intercellular Signaling Peptides and Proteins genetics, Leucine chemistry, Male, Mice, Mice, SCID, Middle Aged, Receptors, G-Protein-Coupled genetics, Recombinant Proteins genetics, Recombinant Proteins metabolism, Skin metabolism, Axin Protein genetics, Hair growth & development, Hair Follicle cytology, Stem Cells cytology, Thrombospondins genetics, Wnt Signaling Pathway
- Abstract
Wnt signaling is required for the development of the hair follicle, and for inciting the growth (anagen) phase of the hair cycle. Most strategies to enhance Wnt signaling for hair growth create a state of constitutive Wnt activation, which leads to neoplastic transformation of the epithelial hair matrix. Using Axin2(LacZ/+) and Axin2(Cre/+)R26R(mTmG/+) reporter mice and RNA analyses, we show that Wnt signaling is elevated during anagen, is reduced at the onset of catagen, and can be reamplified in the skin and surrounding hair follicles via intradermal injection of recombinant R-spondin2 protein. Using Lgr5(LacZ/+) reporter mice, we demonstrate that this amplified Wnt environment leads to activation of leucine-rich repeat-containing G-protein coupled receptor 5-positive stem cells in the hair follicle. The onset of catagen is repressed by R-spondin2 injection, and the anagen phase persists. As a consequence, hair shafts grow longer. We conclude that R-spondin2 treatment activates hair follicle stem cells and therefore may have therapeutic potential to promote hair growth., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF