Theranostics 2013; 3(11):841-850. doi:10.7150/thno.6997 This issue Cite
Research Paper
1. Beijing Institute of Transfusion Medicine, 27(9) TaiPing Road, Beijing, China;
2. In vivo Oncology and Pharmacology, Pharmaron, 6 Taihe Road, Beijing, China;
3. Department of Incretology, Navy General Hospital of PLA, Beijing, China.
* These authors contributed equally to this work.
The nuclear factor-κB (NF-κB) signaling pathway plays a critical role in a multitude of cellular processes. Activation of the NF-κB transcription factor family is essential for the initiation of inflammation, immunity, cell proliferation and apoptosis through a list of responsive genes. In hepatic tissue, activation of the NF-κB pathway has been implicated in a number of pathological conditions. Here we described a mouse model for noninvasive quantification of NF-κB activation in the hepatic tissues. Mice were subjected to hydrodynamic delivery with a mixture of pattB-NF-κB-Fluc reporter and φC31o integrase vector. Hepatic expression of φC31o integrase mediated chromosomal integration of the pattB-NF-κB-Fluc reporter, resulting in stable luciferase expression at 300 days post transfection. We applied noninvasive imaging and were able to detect NF-κB activation under acute liver injury and hepatitis conditions. During hepatectomy-induced liver regeneration, NF-κB activation was detected locally in the tissues at the surgery site. Treatment with Sorafenib suppressed NF-κB activation, accompanied with perturbation of liver regeneration. In conclusion, we established a method for stable transfection of the hepatic tissues and applied the transfected mice to longitudinal monitoring of NF-κB activity under pathological conditions. Further exploration of this methodology for establishment of other disease models and for evaluation of novel pharmaceuticals is likely to be fruitful.
Keywords: Nuclear factor-κB, noninvasive molecular imaging, φC31o integrase, Sorafenib, animal model.