Effect of retinoic acid-induced transglutaminase on cell growth in regenerating liver

Transglutaminase 2 (TG2) is implicated in the inhibitory regulation of the hepatocyte growth in vitro. In vivo, however, the role of TG2 in liver regeneration after partial hepatectomy (PH) is almost unknown. A dramatic increase of TG2 expression and activation is induced by retinoic acid (RA). Here we show the effect of the RA-induced overexpression of TG2 on liver regeneration after PH. Regenerating rat liver was prepared by 70% PH. RA was intraperitoneally injected immediately after PH. TG2 activity was determined by incorporation of 14C-putrescine into dimethylcasein. Cell cycle was evaluated for incorporation of BrdU into hepatocytes and detected by a flow cytometric analysis. The treatment of RA greatly increased TG2 activity at 1 day after PH. At that time, DNA synthesis was significantly reduced by the treatment of RA. The recovery of liver weight after PH was significantly delayed by the treatment of RA. These results suggested that TG2 was involved in growth capacity in regenerating rat liver after PH.