TCDD-induced activation of aryl hydrocarbon receptor regulates the skin stem cell population.

Abstract

The environmental toxin 2,3,7,8 tetrachlorodibenzo p-dioxin (TCDD) plays an important role in the development of chloracne. Chloracne is characterized by hyperkeratosis of the interfollicular squamous epithelium and metaplasia of sebaceous glands. Dysregulation of keratinocyte terminal differentiation leading to accelerated formation of the cornified envelope as a result of TCDD-mediated aryl hydrocarbon receptor (AHR) activation has been implicated as one of the molecular pathogenic mechanisms contributing to the development of chloracne. In addition, chloracne is characterized by altered skin stem cell characteristics, and it has been speculated that the phenotype of chloracne closely matches that of c-Myc overexpressing transgenic mice. Therefore, we sought to determine whether TCDD plays a role in regulation of the skin stem cell population. We have proposed in this report that TCDD may directly or indirectly (via AHR receptor cross-talk) upregulate c-Myc via epidermal growth factor receptor-extracellular signal regulated kinase (EGFR-ERK) axis stimulation, which may correspond with an increase in human epidermal stem cell activation and differentiation of EPSCs into keratinocytes, with eventual depletion of the epidermal stem cell compartment of the skin. Thus, TCDD may cause increased epidermal stem cell turnover during chloracne.

• Authors: Chirag Mandavia
• Journal: Medical hypotheses (Med Hypotheses) Vol. 84 Issue 3 Pg. 204-8 (Mar 2015) ISSN: 1532-2777 [Electronic] United States
• PMID: 25618441 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

• MYC protein, human
• Polychlorinated Dibenzodioxins
• Proto-Oncogene Proteins c-myc
• Receptors, Aryl Hydrocarbon
• EGFR protein, human
• ErbB Receptors

Topics

• Cell Differentiation (physiology)
• Chloracne (metabolism)
• ErbB Receptors (metabolism)
• Gene Expression Regulation (drug effects)
• Humans
• MAP Kinase Signaling System (physiology)
• Polychlorinated Dibenzodioxins (toxicity)
• Proto-Oncogene Proteins c-myc (metabolism)
• Receptors, Aryl Hydrocarbon (metabolism)
• Skin (cytology, pathology)
• Stem Cells (metabolism, physiology)