Brunner Magdalena A T, Jagannathan Vidhya, Waluk Dominik P, Roosje Petra, Linek Monika, Panakova Lucia, Leeb Tosso, Wiener Dominique J, Welle Monika M
Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
DermFocus, University of Bern, Bern, Switzerland.
PLoS One. 2017 Oct 24;12(10):e0186469. doi: 10.1371/journal.pone.0186469. eCollection 2017.
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.
X型脱毛症是博美犬的一种毛囊生长周期停滞性疾病。组织学上，静止期和休止期毛囊占主导，而生长期毛囊稀少。生长期的诱导依赖于毛囊干细胞的激活及其随后的增殖和分化。干细胞功能取决于信号分子和转录因子的精细调控相互作用，而在犬类中这些作用尚未明确。我们对皮肤活检样本进行了转录组分析，以研究X型脱毛症中分子通路的改变。对5只患病和4只未患病的博美犬的活检样本进行了研究。差异基因表达显示Wnt（CTNNB1、LEF1、TCF3、WNT10B）和Shh（SHH、GLI1、SMO、PTCH2）通路的关键调节基因下调。在小鼠中已表明，Wnt和Shh信号传导可导致干细胞激活和分化。因此，我们的研究结果与X型脱毛症犬缺乏生长期毛囊一致。我们还观察到干细胞标志物SOX9、LHX2、LGR5、TCF7L1和GLI1显著下调，而静止标志物NFATc1在X型脱毛症中上调。此外，在X型脱毛症中，直接参与性激素代谢的酶（CYP1A1、CYP1B1、HSD17B14）的编码基因受到差异调节。这些发现与目前关于该疾病中性激素代谢失调的提议一致，但尚未得到证实。
