Intrinsic hepatocyte dedifferentiation is accompanied with upregulation of mesenchymal markers. (A) Time course of cultured hepatocytes stained with phalloidin. Starting on day 2, hepatocytes loose polar structure. Lower panel shows cells treated with TGF-β1 leading to similar actin remodeling and reduced cell-cell contacts over time. (B) Western blot showing a time course of murine hepatocytes cultured in monolayer on a stiff collagen matrix. Mesenchymal markers are induced and AKT and ERK signaling pathways are activated over time. Caveolin-1 is strongly upregulated during culture. (C) Collagen 1α1 (p < 0.001 at d3 and d4) and (D) caveolin-1 mRNA (p < 0.001 at d3 and d4) are upregulated in culture over time.