A20 Role in Liver regeneration

Genome wide transcriptional profiling on liver mRNA retrieved from recombinant adenovirus A20 (rAd.A20) and rAd.bgalactosidase transduced livers, before and 24 hours after 78% extended liver resection. Overexpression of the NF-kB inhibitory protein A20 improves recovery of liver function and mass following extended liver resection and severe liver ischemia reperfusion injury in mice. In this project, we explored effects of A20 using transcriptional profiling on liver mRNA retrieved from recombinant adenovirus A20 (rAd.A20) and rAd.bgalactosidase transduced livers, before and 24 hours after 78% extended liver resection. A20 or beta-galactosidase gene expression in the mouse liver was achieved by penile vein injection of 1x109 pfu of rAd. in 100uL of normal saline, which results in optimal transgene expression 5 days after injection in 30% to 40% of hepatocytes (Longo et al, 2005). Extended (78%) LR, consisting of resection of the lateral, medial, left, and right lobes, was performed 5 days following rAd. administration in 8-week old BALB/c mice weighing 25 to 30 grams (Taconic, Germantown, NY), as described (Longo et al, 2005). RNA was extracted from the resected portion of the liver (before samples) and from the remnant liver 24 hours after resection (after samples). RNA from three animals was pooled per microarray and 2 microarrays per group were performed.