Bone morphogenetic protein signaling regulates the size of hair follicles and modulates the expression of cell cycle-associated genes

Details

Serval ID
serval:BIB_DC45F62F57C4
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Bone morphogenetic protein signaling regulates the size of hair follicles and modulates the expression of cell cycle-associated genes
Journal
Proceedings of the National Academy of Sciences of the United States of America
Author(s)
Sharov  A. A., Sharova  T. Y., Mardaryev  A. N., Tommasi di Vignano  A., Atoyan  R., Weiner  L., Yang  S., Brissette  J. L., Dotto  G. P., Botchkarev  V. A.
ISSN
0027-8424 (Print)
Publication state
Published
Issued date
11/2006
Volume
103
Number
48
Pages
18166-71
Notes
Journal Article
Research Support, N.I.H., Extramural --- Old month value: Nov 28
Abstract
Bone morphogenetic protein (BMP) signaling is involved in the regulation of a large variety of developmental programs, including those controlling organ sizes. Here, we show that transgenic (TG) mice overexpressing the BMP antagonist noggin (promoter, K5) are characterized by a marked increase in size of anagen hair follicles (HFs) and by the replacement of zig-zag and auchen hairs by awl-like hairs, compared with the age-matched WT controls. Markedly enlarged anagen HFs of TG mice show increased proliferation in the matrix and an increased number of hair cortex and medulla cells compared with WT HFs. Microarray and real-time PCR analyses of the laser-captured hair matrix cells show a strong decrease in expression of Cdk inhibitor p27(Kip1) and increased expression of selected cyclins in TG vs. WT mice. Similar to TG mice, p27(Kip1) knockout mice also show an increased size of anagen HFs associated with increased cell proliferation in the hair bulb. Primary epidermal keratinocytes (KC) from TG mice exhibit significantly increased proliferation and decreased p27(Kip1) expression, compared with WT KC. Alternatively, activation of BMP signaling in HaCaT KC induces growth arrest, stimulates p27(Kip1) expression, and positively regulates p27(Kip1) promoter activity, thus further supporting a role of p27(Kip1) in mediating the effects of BMP signaling on HF size. These data suggest that BMP signaling plays an important role in regulating cell proliferation and controls the size of anagen HFs by modulating the expression of cell-cycle-associated genes in hair matrix KC.
Keywords
Animals Bone Morphogenetic Proteins/genetics/*metabolism Carrier Proteins/genetics/metabolism Cell Cycle Proteins/*genetics Cell Proliferation Cyclin-Dependent Kinase Inhibitor p27/deficiency/genetics/metabolism *Gene Expression Regulation, Developmental Hair/cytology/metabolism Hair Follicle/*cytology/growth & development/*metabolism Keratinocytes/cytology/metabolism Mice Mice, Transgenic *Signal Transduction
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 15:58
Last modification date
20/08/2019 17:01
Usage data