Wnt信号通路
头发周期
胶质1
LGR5型
下调和上调
毛囊
生物
干细胞
细胞生物学
转录组
内分泌学
细胞分化
内科学
癌症研究
信号转导
刺猬信号通路
基因表达
遗传学
基因
医学
作者
Magdalena A. T. Brunner,Vidhya Jagannathan,Dominik P. Waluk,Petra Roosje,Моника Линек,Lucia Panakova,Tosso Leeb,Dominique J Wiener,Monika Welle
出处
期刊:PLOS ONE
[Public Library of Science]
日期:2017-10-24
卷期号:12 (10): e0186469-e0186469
被引量:23
标识
DOI:10.1371/journal.pone.0186469
摘要
Alopecia X is a hair cycle arrest disorder in Pomeranians. Histologically, kenogen and telogen hair follicles predominate, whereas anagen follicles are sparse. The induction of anagen relies on the activation of hair follicle stem cells and their subsequent proliferation and differentiation. Stem cell function depends on finely tuned interactions of signaling molecules and transcription factors, which are not well defined in dogs. We performed transcriptome profiling on skin biopsies to analyze altered molecular pathways in alopecia X. Biopsies from five affected and four non-affected Pomeranians were investigated. Differential gene expression revealed a downregulation of key regulator genes of the Wnt (CTNNB1, LEF1, TCF3, WNT10B) and Shh (SHH, GLI1, SMO, PTCH2) pathways. In mice it has been shown that Wnt and Shh signaling results in stem cell activation and differentiation Thus our findings are in line with the lack of anagen hair follicles in dogs with Alopecia X. We also observed a significant downregulation of the stem cell markers SOX9, LHX2, LGR5, TCF7L1 and GLI1 whereas NFATc1, a quiescence marker, was upregulated in alopecia X. Moreover, genes coding for enzymes directly involved in the sex hormone metabolism (CYP1A1, CYP1B1, HSD17B14) were differentially regulated in alopecia X. These findings are in agreement with the so far proposed but not yet proven deregulation of the sex hormone metabolism in this disease.
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