Regenerative growth is impacted by TCDD: gene expression analysis reveals extracellular matrix modulation.

TitleRegenerative growth is impacted by TCDD: gene expression analysis reveals extracellular matrix modulation.
Publication TypeJournal Article
Year of Publication2006
AuthorsAndreasen, EA, Mathew, LK, Tanguay, RL
JournalToxicol Sci
Date Published2006 Jul
KeywordsAnimals, Base Sequence, DNA Primers, Extracellular Matrix, Gene Expression Profiling, Male, Polychlorinated Dibenzodioxins, Regeneration, Reverse Transcriptase Polymerase Chain Reaction, Zebrafish

Adult zebrafish can completely regenerate their caudal fin following amputation. This complex process is initiated by the formation of an epithelial wound cap over the amputation site by 12 h post amputation (hpa). Once the cap is formed, mesenchymal cells proliferate and migrate from sites distal to the wound plane and accumulate under the epithelial cap forming the blastemal structure within 48 hpa. Blastemal cells proliferate and differentiate, replacing the amputated tissues, which are populated with angiogenic vessels and innervating nerves during the regenerative outgrowth phase which is completed around 14 days post amputation (dpa). Regenerative outgrowth does not occur in TCDD-exposed zebrafish. To identify the molecular pathways that are perturbed by TCDD exposure, male zebrafish were ip injected with 50 ng/g TCDD or vehicle and caudal fins were amputated. Regenerating fin tissue was collected at 1, 3, and 5 dpa for mRNA abundance analysis. Microarray analysis and quantitative real time PCR revealed that wound healing and regeneration alone altered the expression of nearly 900 genes by at least two-fold between 1 and 5 dpa. TCDD altered the abundance of 370 genes at least two-fold. Among these, several known aryl hydrocarbon responsive genes were identified in addition to several genes involved in extracellular matrix composition and metabolism. The profile of misexpressed genes is suggestive of impaired cellular differentiation and extracellular matrix composition potentially regulated by Sox9b.

Alternate JournalToxicol. Sci.
PubMed ID16443690
Grant ListES 10820 / ES / NIEHS NIH HHS / United States
ES 03850 / ES / NIEHS NIH HHS / United States
ES 00210 / ES / NIEHS NIH HHS / United States
R01 ES010820 / ES / NIEHS NIH HHS / United States
P30 ES000210 / ES / NIEHS NIH HHS / United States