Aryl hydrocarbon receptor activation impairs extracellular matrix remodeling during zebra fish fin regeneration

Toxicol Sci. 2007 Jan;95(1):215-26. doi: 10.1093/toxsci/kfl119. Epub 2006 Sep 26.


Adult zebra fish completely regenerate their caudal (tail) fin following partial amputation. Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) inhibits this regenerative process. Proper regulation of transcription, innervation, vascularization, and extracellular matrix (ECM) composition is essential for complete fin regeneration. Previous microarray studies suggest that genes involved in ECM regulation are misexpressed following activation of the aryl hydrocarbon receptor. To investigate whether TCDD blocks regeneration by impairing ECM remodeling, male zebra fish were i.p. injected with 50 ng/g TCDD or vehicle, and caudal fins were amputated. By 3 days postamputation (dpa), the vascular network in the regenerating fin of TCDD-exposed fish was disorganized compared to vehicle-exposed animals. Furthermore, immunohistochemical staining revealed that axonal outgrowth was impacted by TCDD as early as 3 dpa. Histological analysis demonstrated that TCDD exposure leads to an accumulation of collagen at the end of the fin ray just distal to the amputation site by 3 dpa. Mature lepidotrichial-forming cells (fin ray-forming cells) were not observed in the fins of TCDD-treated fish. The capacity to metabolize ECM was also altered by TCDD exposure. Quantitative real-time PCR studies revealed that the aryl hydrocarbon pathway is active and that matrix-remodeling genes are expressed in the regenerate following TCDD exposure.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Carcinogens, Environmental / toxicity*
  • Collagen / metabolism
  • Cytochrome P-450 CYP1A1 / biosynthesis
  • Electrophoresis, Polyacrylamide Gel
  • Enzyme Induction / drug effects
  • Extracellular Matrix / metabolism*
  • Extremities / anatomy & histology
  • Extremities / physiology
  • Gene Expression Regulation / drug effects
  • Immunohistochemistry
  • Male
  • Matrix Metalloproteinases / metabolism
  • Polychlorinated Dibenzodioxins / toxicity*
  • Polymerase Chain Reaction
  • Proteoglycans / metabolism
  • RNA, Messenger / metabolism
  • Receptors, Aryl Hydrocarbon / agonists*
  • Receptors, Aryl Hydrocarbon / metabolism
  • Regeneration / drug effects*
  • Time Factors
  • Tissue Plasminogen Activator / metabolism
  • Transforming Growth Factor beta1 / metabolism
  • Wound Healing / drug effects*
  • Zebrafish / metabolism
  • Zebrafish / physiology*
  • Zebrafish Proteins / metabolism*


  • Carcinogens, Environmental
  • Polychlorinated Dibenzodioxins
  • Proteoglycans
  • RNA, Messenger
  • Receptors, Aryl Hydrocarbon
  • Transforming Growth Factor beta1
  • Zebrafish Proteins
  • Collagen
  • Cytochrome P-450 CYP1A1
  • Tissue Plasminogen Activator
  • Matrix Metalloproteinases