Andreasen Eric A, Mathew Lijoy K, Löhr Christiane V, Hasson Rachelle, Tanguay Robert L
Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, Oregon 97331-7301, USA.
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.
成年斑马鱼在部分截肢后能完全再生其尾鳍。暴露于2,3,7,8-四氯二苯并对二恶英（TCDD）会抑制这一再生过程。转录、神经支配、血管生成和细胞外基质（ECM）组成的适当调节对于鳍的完全再生至关重要。先前的微阵列研究表明，参与ECM调节的基因在芳烃受体激活后表达异常。为了研究TCDD是否通过损害ECM重塑来阻断再生，将雄性斑马鱼腹腔注射50 ng/g TCDD或溶剂，然后进行尾鳍截肢。在截肢后3天（dpa），与暴露于溶剂的动物相比，暴露于TCDD的鱼再生鳍中的血管网络紊乱。此外，免疫组织化学染色显示，早在3 dpa时轴突生长就受到TCDD的影响。组织学分析表明，到3 dpa时，TCDD暴露导致截肢部位远端鳍条末端胶原积累。在TCDD处理的鱼的鳍中未观察到成熟的鳞质形成细胞（鳍条形成细胞）。TCDD暴露也改变了代谢ECM的能力。定量实时PCR研究表明，芳烃途径活跃，TCDD暴露后再生组织中表达基质重塑基因。
