Growth and differentiation of rat hepatocytes: changes in transcription factors HNF-3, HNF-4, STAT-3, and STAT-5.

The liver enriched transcription factors HNF-3 and HNF-4 are known to play major roles in development and differentiation of hepatocytes. STAT-3 and STAT-5 are signaling peptides activated by a variety of cytokines and growth factors including HGF and EGF. Their role in hepatocyte growth and differentiation is yet to be determined. We examined protein expression and DNA binding activities of these transcription factors in a hepatocyte culture system in which the hepatocytes first de-differentiate and proliferate. Overlaying proliferating hepatocytes with EHS-matrix led to an increase in HNF-4 protein and DNA-binding activity. STAT-5 DNA binding activity was only slightly effected by EHS-matrix. HNF-3 and STAT-3 DNA-binding activities were reduced in the presence of EHS-matrix. This is consistent with the role of HNF-3 as the major initiating transcription factor involved in embryonic liver development and suggests, that STAT-3 might also play a role in growth and differentiation of hepatocytes.