Modulation of connexins during differentiation of oval cells into hepatocytes

The connexins are a family of related gap-junction proteins, implicated in embryonic development, cell growth control, and cellular differentiation. To identify connexins involved in liver cell differentiation, both in vivo and in vitro systems were employed to study expression of connexins 26, 32, and 43. Northern blot analysis and in situ hybridization were used to measure the levels of connexin expression and cellular localization of the transcripts, respectively. Normal liver expressed high connexin 32, low connexin 26, and barely detectable connexin 43. In vivo proliferation and differentiation of oval cells was at first accompanied by increased connexin 43 and decreased connexin 32 expression; later as the oval cells differentiated into hepatocytes, connexin 43 disappeared and connexin 32 increased to control levels. In situ hybridization showed that both oval cells and bile duct epithelial cells, but not hepatocytes, expressed connexin 43. A switch from connexin 43 to connexin 32 expression was observed following in vitro transformation and differentiation of rat liver epithelial cells toward the hepatocytic lineage. These results suggest that early progenitor cells in the liver express connexin 43 and a switch from connexin 43 to connexin 32 may signal commitment to hepatocytic differentiation.