The response of rat liver perisinusoidal lipocytes to polypeptide growth regulator changes with their transdifferentiation into myofibroblast-like cells in culture.

During culture on uncoated plastic wells rat liver perisinusoidal lipocytes change their differentiated phenotype (transdifferentiate) within 1-2 weeks and obtain a myofibroblast-like phenotype (myofibroblast-like cells). This transdifferentiation was documented by morphologic (loss of fat droplets, flat cell shape, cytoplasmic extensions, expression of iso-alpha smooth muscle actin) and biochemical criteria (loss of retinyl-palmitate, enhanced matrix synthesis). Whereas transforming growth factor alpha (TGF alpha) stimulated and transforming growth factor beta (TGF beta 1) inhibited the proliferation of perisinusoidal lipocytes (early culture) these cytokines did not effect the growth of the myofibroblast-like cells. Opposite effects were obtained with platelet-derived growth factor (PDGF) which stimulated the growth of myofibroblast-like cells only. Insulin-like growth factor (IGF1) was mitogenic in both perisinusoidal lipocytes and myofibroblast-like cells, respectively. Furthermore, whereas the expression of the mRNAs of decorin and biglycan was stimulated by TGF beta 1 in perisinusoidal lipocytes, the synthesis of these mRNAs was stimulated in myofibroblast-like cells predominantly by TGF alpha. Similar effects of TGF alpha and TGF beta 1 have been observed on the glycosaminoglycan-([35S]sulfate incorporation) and proteoglycan level ([3H]leucin incorporation into decorin and biglycan). Neither IGF1 and PDGF stimulated glycosaminoglycan synthesis in perisinusoidal lipocytes or in myofibroblast-like cells. The results demonstrate that the effects of the polypeptide growth regulators TGF alpha, TGF beta 1 and PDGF depend on the cell phenotype (stage of cell activation/transdifferentiation) and may be completely different in perisinusoidal lipocytes and its transformed counterpart the myofibroblast-like cells.