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

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 ce...

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Autores principales: Brunner, Magdalena A. T., Jagannathan, Vidhya, Waluk, Dominik P., Roosje, Petra, Linek, Monika, Panakova, Lucia, Leeb, Tosso, Wiener, Dominique J., Welle, Monika M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655477/
https://www.ncbi.nlm.nih.gov/pubmed/29065140
http://dx.doi.org/10.1371/journal.pone.0186469
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author Brunner, Magdalena A. T.
Jagannathan, Vidhya
Waluk, Dominik P.
Roosje, Petra
Linek, Monika
Panakova, Lucia
Leeb, Tosso
Wiener, Dominique J.
Welle, Monika M.
author_facet Brunner, Magdalena A. T.
Jagannathan, Vidhya
Waluk, Dominik P.
Roosje, Petra
Linek, Monika
Panakova, Lucia
Leeb, Tosso
Wiener, Dominique J.
Welle, Monika M.
author_sort Brunner, Magdalena A. T.
collection PubMed
description 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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spelling pubmed-56554772017-11-09 Novel insights into the pathways regulating the canine hair cycle and their deregulation in alopecia X Brunner, Magdalena A. T. Jagannathan, Vidhya Waluk, Dominik P. Roosje, Petra Linek, Monika Panakova, Lucia Leeb, Tosso Wiener, Dominique J. Welle, Monika M. PLoS One Research Article 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. Public Library of Science 2017-10-24 /pmc/articles/PMC5655477/ /pubmed/29065140 http://dx.doi.org/10.1371/journal.pone.0186469 Text en © 2017 Brunner et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Brunner, Magdalena A. T.
Jagannathan, Vidhya
Waluk, Dominik P.
Roosje, Petra
Linek, Monika
Panakova, Lucia
Leeb, Tosso
Wiener, Dominique J.
Welle, Monika M.
Novel insights into the pathways regulating the canine hair cycle and their deregulation in alopecia X
title Novel insights into the pathways regulating the canine hair cycle and their deregulation in alopecia X
title_full Novel insights into the pathways regulating the canine hair cycle and their deregulation in alopecia X
title_fullStr Novel insights into the pathways regulating the canine hair cycle and their deregulation in alopecia X
title_full_unstemmed Novel insights into the pathways regulating the canine hair cycle and their deregulation in alopecia X
title_short Novel insights into the pathways regulating the canine hair cycle and their deregulation in alopecia X
title_sort novel insights into the pathways regulating the canine hair cycle and their deregulation in alopecia x
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655477/
https://www.ncbi.nlm.nih.gov/pubmed/29065140
http://dx.doi.org/10.1371/journal.pone.0186469
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