Zonal differences in effects of HGF/SF and EGF on DNA synthesis in hepatocytes at different times post-hepatectomy

Abstract

This study was done for investigation of the DNA synthesis induced by HGF/SF and EGF in periportal hepatocytes (PPH) and perivenous hepatocytes (PVH) isolated at different times post-hepatectomy. Preparation, culture, and DNA synthesis of PPH and PVH were done as previously described. In both PPH and PVH isolated at 6 and 12 h post-hepatectomy, the maximum DNA synthesis induced by both HGF/SF and EGF was observed from 24 to 48 h post-hepatectomy. In contrast, in both types of hepatocytes isolated at 36, 72 and 96 h, 1 and 2 weeks, and 1 month post-hepatectomy, maximum DNA synthesis was observed from 48 to 72 h. However, maximum DNA synthesis induced by HGF/SF and EGF was at its lowest in PPH isolated at 12 h and PVH isolated at 6 h post-hepatectomy. Maximum DNA synthesis returned to the control level in PPH and PVH isolated at 72 and 96 h post-hepatectomy, respectively. Specific binding studies using [ 125 I ] HGF/SF and [ 125 I ] EGF supported the above data. From these data, it was demonstrated that first, the PPH and PVH cell cycles have the same post-hepatectomy, but are dependent on the preparation time. Secondly, differences in DNA synthesis in PPH and PVH post-hepatectomy suggest that liver regeneration may occur unevenly.