PROLIFERATION-ASSOCIATED DIFFERENCES IN THE SPATIAL AND TEMPORAL EXPRESSION OF GAP JUNCTION GENES IN RAT-LIVER

After a 70% partial hepatectomy (PH), the steady-state levels of Conne xin (Cx)32, Cx26, and Cx43 messenger RNA (mRNA) transcripts each displ ayed unique patterns of temporal expression. Within 1 hour after surgi cal resection, increased expression of all three Cx mRNAs was observed , Subsequently, the level of Cx32 mRNA transcripts transiently decreas ed to a nadir at 12 hours. Comparisons of the spatial changes with pre viously reported hepatocyte proliferation kinetics induced by PH demon strated that hepatocytes before S-phase ''remodel'' their GJs, Within 1 to 5 hours post-PH, midzonal hepatocytes exhibited diffuse membrane staining different from the normal punctate distribution. Subsequently , midzonal hepatocytes expressed co-localized punctate Cx32 and Cx26 i mmunostaining. Because the changes occurred in midzonal hepatocytes be fore 24 hours post-PH, near the peak of hepatocyte DNA synthesis, thes e findings indicate that Cx26 is enhanced in hepatocytes before the on set of S-phase. In contrast to the restricted expression of Cx43 in Gl isson's capsule in adult liver, Cx43 protein and mRNA were enhanced sp ecifically in proliferating bile duct and perisinusoidal cells post-PH . PH performed during continuous administration of 2-acetylaminofluore ne (AAF) prevented changes in Cx32 and Cx26 staining observed in the a bsence of AAF, Proliferating oval cells were found to express diffuse Cx43 immunoreactivity, On day 11 post-PH and AAF, basophilic hepatocyt es displayed both punctate Cx32 and Cx26 staining, whereas bile ducts and perisinusoidal cells expressed Cx43. These findings indicate that alterations in Cx32 and Cx26 expression occur rapidly in hepatocytes s timulated to proliferate and that several nonparenchymal liver cell. t ypes upregulate Cx43 expression when induced to proliferate, Different iation of oval cells into basophilic hepatocytes resulted in their exp ression of Cx32 and Cx26.