We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-mediated deregulation of myeloid and sebaceous gland stem/progenitor cell homeostasis.
- Authors
Bock, Karl
- Abstract
Studies of TCDD toxicity stimulated identification of the responsible aryl hydrocarbon receptor (AHR), a multifunctional, ligand-activated transcription factor of the basic helix-loop-helix/Per-Arnt-Sim family. Accumulating evidence suggests a role of this receptor in homeostasis of stem/progenitor cells, in addition to its known role in xenobiotic metabolism. (1) Regulation of myelopoiesis is complex. As one example, AHR-mediated downregulation of human CD34+ progenitor differentiation to monocytes/macrophages is discussed. (2) Accumulation of TCDD in sebum leads to deregulation of sebocyte differentiation via Blimp1-mediated inhibition of c-Myc signaling and stimulation of Wnt-mediated proliferation of interfollicular epidermis. The resulting sebaceous gland atrophy and formation of dermal cysts may explain the pathogenesis of chloracne, the hallmark of TCDD toxicity. (3) TCDD treatment of confluent liver stem cell-like rat WB-F344 cells leads to release from cell-cell contact inhibition via AHR-mediated crosstalk with multiple signaling pathways. Further work is needed to delineate AHR function in crosstalk with other signaling pathways.
- Subjects
TETRACHLORODIBENZODIOXIN; SEBACEOUS glands; HOMEOSTASIS; PROGENITOR cells; STEM cells; TOXICITY testing; ARYL hydrocarbon receptors; PHYSIOLOGY
- Publication
Archives of Toxicology, 2017, Vol 91, Issue 6, p2295
- ISSN
0340-5761
- Publication type
Article
- DOI
10.1007/s00204-017-1965-2