Cargando…

Coactivator MED1 Ablation in Keratinocytes Results in Hair Cycling Defects and Epidermal Alternations

The transcriptional coactivator complex Mediator facilitates transcription of nuclear hormone receptors and other transcription factors. We have previously isolated the Mediator complex from primary keratinocytes as the vitamin D receptor interacting protein complex. We identified a role for Mediato...

Descripción completa

Detalles Bibliográficos
Autores principales: Oda, Yuko, Hu, Lizhi, Bul, Vadim, Elalieh, Hashem, Reddy, Janardan K., Bikle, Daniel D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3400544/
https://www.ncbi.nlm.nih.gov/pubmed/22189783
http://dx.doi.org/10.1038/jid.2011.430
_version_ 1782238496853852160
author Oda, Yuko
Hu, Lizhi
Bul, Vadim
Elalieh, Hashem
Reddy, Janardan K.
Bikle, Daniel D.
author_facet Oda, Yuko
Hu, Lizhi
Bul, Vadim
Elalieh, Hashem
Reddy, Janardan K.
Bikle, Daniel D.
author_sort Oda, Yuko
collection PubMed
description The transcriptional coactivator complex Mediator facilitates transcription of nuclear hormone receptors and other transcription factors. We have previously isolated the Mediator complex from primary keratinocytes as the vitamin D receptor interacting protein complex. We identified a role for Mediator in keratinocyte proliferation and differentiation in cultured keratinocytes. Here, we investigated the in vivo role of Mediator by generating conditional null mice, where a critical subunit of the Mediator complex, MED1, is deleted from their keratinocytes. The MED1 ablation resulted in aberrant hair differentiation and cycling leading to hair loss. During the first hair follicle cycle, MED1 deletion resulted in a rapid regression of the hair follicles. Hair differentiation was reduced, and β-catenin/vitamin D receptor (VDR) regulated gene expression was dramatically decreased. In the subsequent adult hair cycle, MED1 ablation activated the initiation of hair follicle cycling. Shh signaling was increased, but terminal differentiation was not sufficient. Deletion of MED1 also caused hyper-proliferation of interfollicular epidermal keratinocytes, and increased the expression of epidermal differentiation markers. These results indicate that MED1 plays a critical role in regulating hair/epidermal proliferation and differentiation.
format Online
Article
Text
id pubmed-3400544
institution National Center for Biotechnology Information
language English
publishDate 2011
record_format MEDLINE/PubMed
spelling pubmed-34005442012-10-01 Coactivator MED1 Ablation in Keratinocytes Results in Hair Cycling Defects and Epidermal Alternations Oda, Yuko Hu, Lizhi Bul, Vadim Elalieh, Hashem Reddy, Janardan K. Bikle, Daniel D. J Invest Dermatol Article The transcriptional coactivator complex Mediator facilitates transcription of nuclear hormone receptors and other transcription factors. We have previously isolated the Mediator complex from primary keratinocytes as the vitamin D receptor interacting protein complex. We identified a role for Mediator in keratinocyte proliferation and differentiation in cultured keratinocytes. Here, we investigated the in vivo role of Mediator by generating conditional null mice, where a critical subunit of the Mediator complex, MED1, is deleted from their keratinocytes. The MED1 ablation resulted in aberrant hair differentiation and cycling leading to hair loss. During the first hair follicle cycle, MED1 deletion resulted in a rapid regression of the hair follicles. Hair differentiation was reduced, and β-catenin/vitamin D receptor (VDR) regulated gene expression was dramatically decreased. In the subsequent adult hair cycle, MED1 ablation activated the initiation of hair follicle cycling. Shh signaling was increased, but terminal differentiation was not sufficient. Deletion of MED1 also caused hyper-proliferation of interfollicular epidermal keratinocytes, and increased the expression of epidermal differentiation markers. These results indicate that MED1 plays a critical role in regulating hair/epidermal proliferation and differentiation. 2011-12-22 2012-04 /pmc/articles/PMC3400544/ /pubmed/22189783 http://dx.doi.org/10.1038/jid.2011.430 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Oda, Yuko
Hu, Lizhi
Bul, Vadim
Elalieh, Hashem
Reddy, Janardan K.
Bikle, Daniel D.
Coactivator MED1 Ablation in Keratinocytes Results in Hair Cycling Defects and Epidermal Alternations
title Coactivator MED1 Ablation in Keratinocytes Results in Hair Cycling Defects and Epidermal Alternations
title_full Coactivator MED1 Ablation in Keratinocytes Results in Hair Cycling Defects and Epidermal Alternations
title_fullStr Coactivator MED1 Ablation in Keratinocytes Results in Hair Cycling Defects and Epidermal Alternations
title_full_unstemmed Coactivator MED1 Ablation in Keratinocytes Results in Hair Cycling Defects and Epidermal Alternations
title_short Coactivator MED1 Ablation in Keratinocytes Results in Hair Cycling Defects and Epidermal Alternations
title_sort coactivator med1 ablation in keratinocytes results in hair cycling defects and epidermal alternations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3400544/
https://www.ncbi.nlm.nih.gov/pubmed/22189783
http://dx.doi.org/10.1038/jid.2011.430
work_keys_str_mv AT odayuko coactivatormed1ablationinkeratinocytesresultsinhaircyclingdefectsandepidermalalternations
AT hulizhi coactivatormed1ablationinkeratinocytesresultsinhaircyclingdefectsandepidermalalternations
AT bulvadim coactivatormed1ablationinkeratinocytesresultsinhaircyclingdefectsandepidermalalternations
AT elaliehhashem coactivatormed1ablationinkeratinocytesresultsinhaircyclingdefectsandepidermalalternations
AT reddyjanardank coactivatormed1ablationinkeratinocytesresultsinhaircyclingdefectsandepidermalalternations
AT bikledanield coactivatormed1ablationinkeratinocytesresultsinhaircyclingdefectsandepidermalalternations