Involvement of retinoic acid‐induced transglutaminase activity in zonal differences of hepatocyte proliferation after partial hepatectomy

Abstract

The authors have recently demonstrated that there is inverse correlation between transglutaminase (TGase) activity and DNA synthesis in periportal hepatocytes (PPH) and perivenous hepatocytes (PVH) at 1 day after partial hepatectomy in rats. In order to ensure the involvement of TGase in the differential growth capacities between periportal and perivenous regions of regenerating liver, the aim of this study was to investigate the effect of retinoic acid, an inducer of TGase expression, on zonal differences of hepatocyte proliferation between PPH and PVH isolated from regenerating rat liver. Regenerating liver was prepared by 70% partial hepatectomy. PPH and PVH subpopulations were isolated by the digitonin/collagenase perfusion technique. Cell cycle was evaluated for incorporation of BrdU into hepatocytes and detected by flow cytometric analysis. TGase activity was determined by incorporation of 14C-putrescine into dimethylcasein. When retinoic acid was injected immediately after partial hepatectomy, TGase activity greatly increased in both PPH and PVH at 1 day after partial hepatectomy, and activity was higher in PPH than in PVH. DNA synthesis in both subpopulations did not increase 1 day after partial hepatectomy, with peaks of DNA synthesis shifting to 2 days, and synthesis was higher in PVH than in PPH. These results suggest that TGase might be involved in differential growth capacities between periportal and perivenous regions of regenerating rat liver after partial hepatectomy.