Novel insights into the pathways regulating the canine hair cycle and their deregulation in alopecia X

Magdalena A T Brunner; Vidhya Jagannathan; Dominik P Waluk; Petra Roosje; Monika Linek; Lucia Panakova; Tosso Leeb; Dominique J Wiener; Monika M Welle

doi:10.1371/journal.pone.0186469

Novel insights into the pathways regulating the canine hair cycle and their deregulation in alopecia X

PLoS One. 2017 Oct 24;12(10):e0186469. doi: 10.1371/journal.pone.0186469. eCollection 2017.

Authors

Magdalena A T Brunner^{1

2}, Vidhya Jagannathan³, Dominik P Waluk^{2

4}, Petra Roosje^{2

5}, Monika Linek⁶, Lucia Panakova⁷, Tosso Leeb^{2

3}, Dominique J Wiener^{1

2}, Monika M Welle^{1

2}

Affiliations

¹ Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
² DermFocus, University of Bern, Bern, Switzerland.
³ Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
⁴ Department of Clinical Research, Molecular Dermatology and Stem Cell Research, University of Bern, Bern, Switzerland.
⁵ Division of Clinical Dermatology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
⁶ AniCura Tierärztliche Spezialisten, Hamburg, Germany.
⁷ Clinics of Small Animals and Horses, University of Veterinary Medicine, Vienna, Austria.

Abstract

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.

MeSH terms

Alopecia / genetics
Alopecia / veterinary*
Animals
Biomarkers / metabolism
Dogs
Female
Hair*
Male
Receptors, Calcitriol / metabolism
Stem Cells / metabolism

Substances

Biomarkers
Receptors, Calcitriol

Grants and funding

This study was supported by grants from the Swiss National Science Foundation (CRSII3_160738 / 1) and the International Society for Veterinary Dermatology. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Monika Linek, one of the coauthors, is employed by a private veterinary referral practice (AniCura Tierärztliche Spezialisten). Anicura, provided support in the form of salaries for Monika Linek [ML], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of this author are articulated in the ‘author contributions’ section.