The potential role of transcription factor aryl hydrocarbon receptor in downregulation of hepatic cytochrome P-450 during sepsis

Indoxyl sulfate (IS) is a chronic kidney disease (CKD)-specific renal osteodystrophy metabolite that affects the nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), a transcription factor promoting osteoclastogenesis. However, the mechanisms underlying the regulation of NFATc1 by IS remain unknown. It is intriguing that the Aryl hydrocarbon receptor (AhR) plays a key role in osteoclastogenesis, since IS is an endogenous AhR agonist. This study investigates the relationship between IS concentration and osteoclast differentiation in Raw 264.7 cells, and examines the effects of different IS concentrations on NFATc1 expression through AhR signaling. Our data suggest that both osteoclastogenesis and NFATc1 are affected by IS through AhR signaling in both dose- and time-dependent manners. Osteoclast differentiation increases with short-term, low-dose IS exposure and decreases with long-term, high-dose IS exposure. Different IS levels switch the role of AhR from that of a ligand-activated transcription factor to that of an E3 ubiquitin ligase. We found that the AhR nuclear translocator may play an important role in the regulation of these dual functions of AhR under IS treatment. Altogether, this study demonstrates that the IS/AhR/NFATc1 signaling axis plays a critical role in osteoclastogenesis, indicating a potential role of AhR in the pathology and abnormality of bone turnover in CKD patients.

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Trajectory Shifts in Interdisciplinary Research of the Aryl Hydrocarbon Receptor—A Personal Perspective on Thymus and Skin

International Journal of Molecular Sciences ◽

10.3390/ijms22041844 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1844

Author(s):

Charlotte Esser

Keyword(s):

Transcription Factor ◽

Immune System ◽

Environmental Pollution ◽

Aryl Hydrocarbon Receptor ◽

Interdisciplinary Research ◽

Adaptive Response ◽

Personal Perspective ◽

Aryl Hydrocarbon

Identifying historical trajectories is a useful exercise in research, as it helps clarify important, perhaps even “paradigmatic”, shifts in thinking and moving forward in science. In this review, the development of research regarding the role of the transcription factor “aryl hydrocarbon receptor” (AHR) as a mediator of the toxicity of environmental pollution towards a link between the environment and a healthy adaptive response of the immune system and the skin is discussed. From this fascinating development, the opportunities for targeting the AHR in the therapy of many diseases become clear.

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The Aryl Hydrocarbon Receptor Relays Metabolic Signals to Promote Cellular Regeneration

Stem Cells International ◽

10.1155/2016/4389802 ◽

2016 ◽

Vol 2016 ◽

pp. 1-8 ◽

Cited By ~ 8

Author(s):

Fanny L. Casado

Keyword(s):

Stem Cells ◽

Cell Death ◽

Transcription Factor ◽

Regenerative Medicine ◽

Aryl Hydrocarbon Receptor ◽

Signaling Pathways ◽

Metabolic Efficiency ◽

Aryl Hydrocarbon ◽

Cellular Regeneration

While sensing the cell environment, the aryl hydrocarbon receptor (AHR) interacts with different pathways involved in cellular homeostasis. This review summarizes evidence suggesting that cellular regeneration in the context of aging and diseases can be modulated by AHR signaling on stem cells. New insights connect orphaned observations into AHR interactions with critical signaling pathways such as WNT to propose a role of this ligand-activated transcription factor in the modulation of cellular regeneration by altering pathways that nurture cellular expansion such as changes in the metabolic efficiency rather than by directly altering cell cycling, proliferation, or cell death. Targeting the AHR to promote regeneration might prove to be a useful strategy to avoid unbalanced disruptions of homeostasis that may promote disease and also provide biological rationale for potential regenerative medicine approaches.

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The aryl hydrocarbon receptor and the gut–brain axis

Cellular and Molecular Immunology ◽

10.1038/s41423-020-00585-5 ◽

2021 ◽

Author(s):

Andreia Barroso ◽

João Vitor Mahler ◽

Pedro Henrique Fonseca-Castro ◽

Francisco J. Quintana

Keyword(s):

Transcription Factor ◽

Aryl Hydrocarbon Receptor ◽

Therapeutic Target ◽

Potential Value ◽

Aryl Hydrocarbon ◽

Immune Mediated ◽

Health And Disease

AbstractThe aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor initially identified as the receptor for dioxin. Almost half a century after its discovery, AHR is now recognized as a receptor for multiple physiological ligands, with important roles in health and disease. In this review, we discuss the role of AHR in the gut–brain axis and its potential value as a therapeutic target for immune-mediated diseases.

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Potential role of aryl hydrocarbon receptor signaling in childhood obesity

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids ◽

10.1016/j.bbalip.2020.158714 ◽

2020 ◽

Vol 1865 (8) ◽

pp. 158714 ◽

Cited By ~ 1

Author(s):

Nancy N. Shahin ◽

Ghada T. Abd-Elwahab ◽

Afaf A. Tawfiq ◽

Hanan M. Abdelgawad

Keyword(s):

Childhood Obesity ◽

Aryl Hydrocarbon Receptor ◽

Potential Role ◽

Receptor Signaling ◽

Aryl Hydrocarbon

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Molecular interactions of the aryl hydrocarbon receptor and its biological and toxicological relevance for reproduction

Reproduction ◽

10.1530/rep.1.00294 ◽

2005 ◽

Vol 129 (4) ◽

pp. 379-389 ◽

Cited By ~ 124

Author(s):

P Pocar ◽

B Fischer ◽

T Klonisch ◽

S Hombach-Klonisch

Keyword(s):

Transcription Factor ◽

Aryl Hydrocarbon Receptor ◽

Reproductive Tract ◽

Wide Spectrum ◽

Environmental Pollutants ◽

Large Body ◽

Female Reproductive Tract ◽

Female Reproduction ◽

Aryl Hydrocarbon

The dioxin/aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor responsive to both natural and man-made environmental compounds. AhR and its nuclear partner ARNT are expressed in the female reproductive tract in a variety of species and several indications suggest that the AhR might play a pivotal role in the physiology of reproduction. Furthermore, it appears to be the mediator of most, if not all, the adverse effects on reproduction of a group of highly potent environmental pollutants collectively called aryl hydrocarbons (AHs), including the highly toxic compound 2,3,7,8-tetrachlor-odibenzo-p-dioxin (TCDD). Although a large body of recent literature has implicated AhR in multiple signal transduction pathways, the mechanisms of action resulting in a wide spectrum of effects on female reproduction are largely unknown. Here we summarize the major types of molecular cross-talks that have been identified for the AhR and linked cell signaling pathways and that are relevant for the understanding of the role of this transcription factor in female reproduction.

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