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

Brunner, Magdalena; Jagannathan, Vidhya; Waluk, Dominik Pawel; Roosje, Petra; Linek, Monika; Panakova, Lucia; Leeb, Tosso; Wiener, Dominique Judith; Welle, Monika Maria (2017). Novel insights into the pathways regulating the canine hair cycle and their deregulation in alopecia X. PLoS ONE, 12(10), e0186469. Public Library of Science 10.1371/journal.pone.0186469

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Research Foci > DermFocus
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Dermatology
05 Veterinary Medicine > Department of Clinical Veterinary Medicine (DKV)
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Animal Pathology
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Institute of Genetics
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)
05 Veterinary Medicine > Department of Clinical Veterinary Medicine (DKV) > DKV - Dermatology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Pathologie > Forschungsgruppe Dermatologie
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH)

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Brunner, Magdalena; Jagannathan, Vidya; Waluk, Dominik Pawel; Roosje, Petra; Leeb, Tosso; Wiener, Dominique Judith and Welle, Monika Maria

Subjects:

500 Science > 570 Life sciences; biology
500 Science > 590 Animals (Zoology)
600 Technology > 610 Medicine & health

ISSN:

1932-6203

Publisher:

Public Library of Science

Language:

English

Submitter:

Tosso Leeb

Date Deposited:

06 Dec 2017 09:33

Last Modified:

06 Dec 2017 09:41

Publisher DOI:

10.1371/journal.pone.0186469

PubMed ID:

29065140

BORIS DOI:

10.7892/boris.106655

URI:

https://boris.unibe.ch/id/eprint/106655

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