诺金
细胞生物学
生物
Wnt信号通路
骨形态发生蛋白
BMPR2型
干细胞
祖细胞
信号转导
内分泌学
内科学
遗传学
医学
基因
作者
Jiwang Zhang,Xi He,Wei Tong,Teri N. Johnson,Leanne M. Wiedemann,Yuji Mishina,Jian Feng Ma,Linheng Li
出处
期刊:Stem Cells
[Wiley]
日期:2006-12-01
卷期号:24 (12): 2826-2839
被引量:145
标识
DOI:10.1634/stemcells.2005-0544
摘要
Epithelial stem cells (EP-SCs) located in the bulge region of a hair follicle (HF) have the potential to give rise to hair follicle stem/progenitor cells that migrate down to regenerate HFs. Bone morphogenetic protein (BMP) signaling has been shown to regulate the HF cycle by inhibiting anagen induction. Here we show that active BMP signaling functions to prevent EP-SC activation and expansion. Dynamic expression of Noggin, a BMP antagonist, releases EP-SCs from BMP-mediated restriction, leading to EP-SC activation and initiation of the anagen phase. Experimentally induced conditional inactivation of the BMP type IA receptor (Bmpr1a) in EP-SCs leads to overproduction of HF stem/progenitor cells and the eventual formation of matricomas. This genetic manipulation of the BMP signaling pathway also reveals unexpected activation of beta-catenin, a major mediator of Wnt signaling. We propose that BMP activity controls the HF cycle by antagonizing Wnt/beta-catenin activity. This is at least partially achieved by BMP-mediated enhancement of transforming growth factor-beta-regulated epithelial cell-specific phosphatase (PTEN) function. Subsequently, PTEN, through phosphatidyl inositol 3-kinase-Akt, inhibits the activity of beta-catenin, the convergence point of the BMP and Wnt signaling pathways.
科研通智能强力驱动
Strongly Powered by AbleSci AI