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Delayed Cutaneous Wound Healing and Aberrant Expression of Hair Follicle Stem Cell Markers in Mice Selectively Lacking Ctip2 in Epidermis

BACKGROUND: COUP-TF interacting protein 2 [(Ctip2), also known as Bcl11b] is an important regulator of skin homeostasis, and is overexpressed in head and neck cancer. Ctip2(ep−/−) mice, selectively ablated for Ctip2 in epidermal keratinocytes, exhibited impaired terminal differentiation and delayed...

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Autores principales: Liang, Xiaobo, Bhattacharya, Shreya, Bajaj, Gaurav, Guha, Gunjan, Wang, Zhixing, Jang, Hyo-Sang, Leid, Mark, Indra, Arup Kumar, Ganguli-Indra, Gitali
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3283611/
https://www.ncbi.nlm.nih.gov/pubmed/22383956
http://dx.doi.org/10.1371/journal.pone.0029999
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author Liang, Xiaobo
Bhattacharya, Shreya
Bajaj, Gaurav
Guha, Gunjan
Wang, Zhixing
Jang, Hyo-Sang
Leid, Mark
Indra, Arup Kumar
Ganguli-Indra, Gitali
author_facet Liang, Xiaobo
Bhattacharya, Shreya
Bajaj, Gaurav
Guha, Gunjan
Wang, Zhixing
Jang, Hyo-Sang
Leid, Mark
Indra, Arup Kumar
Ganguli-Indra, Gitali
author_sort Liang, Xiaobo
collection PubMed
description BACKGROUND: COUP-TF interacting protein 2 [(Ctip2), also known as Bcl11b] is an important regulator of skin homeostasis, and is overexpressed in head and neck cancer. Ctip2(ep−/−) mice, selectively ablated for Ctip2 in epidermal keratinocytes, exhibited impaired terminal differentiation and delayed epidermal permeability barrier (EPB) establishment during development, similar to what was observed in Ctip2 null (Ctip2(−/−)) mice. Considering that as an important role of Ctip2, and the fact that molecular networks which underlie cancer progression partially overlap with those responsible for tissue remodeling, we sought to determine the role of Ctip2 during cutaneous wound healing. METHODOLOGY/PRINCIPAL FINDINGS: Full thickness excisional wound healing experiments were performed on Ctip2(L2/L2) and Ctip2(ep−/−) animals per time point and used for harvesting samples for histology, immunohistochemistry (IHC) and immunoblotting. Results demonstrated inherent defects in proliferation and migration of Ctip2 lacking keratinocytes during re-epithelialization. Mutant mice exhibited reduced epidermal proliferation, delayed keratinocyte activation, altered cell-cell adhesion and impaired ECM development. Post wounding, Ctip2(ep−/−) mice wounds displayed lack of E-Cadherin suppression in the migratory tongue, insufficient expression of alpha smooth muscle actin (alpha SMA) in the dermis, and robust induction of K8. Importantly, dysregulated expression of several hair follicle (HF) stem cell markers such as K15, NFATc1, CD133, CD34 and Lrig1 was observed in mutant skin during wound repair. CONCLUSIONS/SIGNIFICANCE: Results confirm a cell autonomous role of keratinocytic Ctip2 to modulate cell migration, proliferation and/or differentiation, and to maintain HF stem cells during cutaneous wounding. Furthermore, Ctip2 in a non-cell autonomous manner regulated granulation tissue formation and tissue contraction during wound closure.
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spelling pubmed-32836112012-03-01 Delayed Cutaneous Wound Healing and Aberrant Expression of Hair Follicle Stem Cell Markers in Mice Selectively Lacking Ctip2 in Epidermis Liang, Xiaobo Bhattacharya, Shreya Bajaj, Gaurav Guha, Gunjan Wang, Zhixing Jang, Hyo-Sang Leid, Mark Indra, Arup Kumar Ganguli-Indra, Gitali PLoS One Research Article BACKGROUND: COUP-TF interacting protein 2 [(Ctip2), also known as Bcl11b] is an important regulator of skin homeostasis, and is overexpressed in head and neck cancer. Ctip2(ep−/−) mice, selectively ablated for Ctip2 in epidermal keratinocytes, exhibited impaired terminal differentiation and delayed epidermal permeability barrier (EPB) establishment during development, similar to what was observed in Ctip2 null (Ctip2(−/−)) mice. Considering that as an important role of Ctip2, and the fact that molecular networks which underlie cancer progression partially overlap with those responsible for tissue remodeling, we sought to determine the role of Ctip2 during cutaneous wound healing. METHODOLOGY/PRINCIPAL FINDINGS: Full thickness excisional wound healing experiments were performed on Ctip2(L2/L2) and Ctip2(ep−/−) animals per time point and used for harvesting samples for histology, immunohistochemistry (IHC) and immunoblotting. Results demonstrated inherent defects in proliferation and migration of Ctip2 lacking keratinocytes during re-epithelialization. Mutant mice exhibited reduced epidermal proliferation, delayed keratinocyte activation, altered cell-cell adhesion and impaired ECM development. Post wounding, Ctip2(ep−/−) mice wounds displayed lack of E-Cadherin suppression in the migratory tongue, insufficient expression of alpha smooth muscle actin (alpha SMA) in the dermis, and robust induction of K8. Importantly, dysregulated expression of several hair follicle (HF) stem cell markers such as K15, NFATc1, CD133, CD34 and Lrig1 was observed in mutant skin during wound repair. CONCLUSIONS/SIGNIFICANCE: Results confirm a cell autonomous role of keratinocytic Ctip2 to modulate cell migration, proliferation and/or differentiation, and to maintain HF stem cells during cutaneous wounding. Furthermore, Ctip2 in a non-cell autonomous manner regulated granulation tissue formation and tissue contraction during wound closure. Public Library of Science 2012-02-21 /pmc/articles/PMC3283611/ /pubmed/22383956 http://dx.doi.org/10.1371/journal.pone.0029999 Text en Liang 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Liang, Xiaobo
Bhattacharya, Shreya
Bajaj, Gaurav
Guha, Gunjan
Wang, Zhixing
Jang, Hyo-Sang
Leid, Mark
Indra, Arup Kumar
Ganguli-Indra, Gitali
Delayed Cutaneous Wound Healing and Aberrant Expression of Hair Follicle Stem Cell Markers in Mice Selectively Lacking Ctip2 in Epidermis
title Delayed Cutaneous Wound Healing and Aberrant Expression of Hair Follicle Stem Cell Markers in Mice Selectively Lacking Ctip2 in Epidermis
title_full Delayed Cutaneous Wound Healing and Aberrant Expression of Hair Follicle Stem Cell Markers in Mice Selectively Lacking Ctip2 in Epidermis
title_fullStr Delayed Cutaneous Wound Healing and Aberrant Expression of Hair Follicle Stem Cell Markers in Mice Selectively Lacking Ctip2 in Epidermis
title_full_unstemmed Delayed Cutaneous Wound Healing and Aberrant Expression of Hair Follicle Stem Cell Markers in Mice Selectively Lacking Ctip2 in Epidermis
title_short Delayed Cutaneous Wound Healing and Aberrant Expression of Hair Follicle Stem Cell Markers in Mice Selectively Lacking Ctip2 in Epidermis
title_sort delayed cutaneous wound healing and aberrant expression of hair follicle stem cell markers in mice selectively lacking ctip2 in epidermis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3283611/
https://www.ncbi.nlm.nih.gov/pubmed/22383956
http://dx.doi.org/10.1371/journal.pone.0029999
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