Bone morphogenetic protein-4 induced rat hepatic progenitor cell (WB-F344 cell) differentiation toward hepatocyte lineage.

Hepatic progenitor cells are local stem cells in the liver and they can be differentiated into either hepatocytes or cholangiocytes depending on different stimulations. These stimulations include extracellular growth factors and intracellular transcription factors. Bone morphogenetic protein 4 (BMP4) is a member of transforming growth factor beta (TGF-beta) superfamily and was first identified as growth factor to induce ectopic bone formation from skeletal muscle. Role of BMP4 in the liver is still unclear especially its role in hepatic progenitor cells (HPCs) differentiation. BMP4 was used to stimulate rat HPCs (WB-F344 cells) and differentiation of WB-F344 cells was investigated by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot analysis. Both adenovirus delivered BMP4 and recombinant BMP4 were able to induce expression of hepatocyte markers such as albumin, TAT-1, and G6Pase but not cholangiocyte markers such as beta4-integrin and CK19. BMP4 induced differentiation of WB-F344 cells toward hepatocytes was mediated by increase in phosphorylation of Smad1 and ERK1/2. Moreover, BMP4 also stimulated expression of transcription factor--C/EBP-alpha, which involved in differentiation of WB-F344 cells toward hepatocytes. BMP4 is able to stimulate WB-F344 cells differentiation toward hepatocyte lineage.