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 lipo cytes change their differentiated phenotype (transdifferentiate) withi n 1-2 weeks and obtain a myofibroblast-like phenotype (myofibroblast-l ike cells). This transdifferentiation was documented by morphologic (l oss of fat droplets, flat cell shape, cytoplasmic extensions, expressi on of iso-alpha smooth muscle actin) and biochemical criteria (loss of retinyl-palmitate, enhanced matrix synthesis). Whereas transforming g rowth factor alpha (TGFalpha) stimulated and transforming growth facto r beta (TGFbeta1) inhibited the proliferation of perisinusoidal lipocy tes (early culture) these cytokines did not effect the growth of the m yofibroblast-like cells. Opposite effects were obtained with platelet- derived growth factor (PDGF) which stimulated the growth of myofibrobl ast-like cells only. Insulin-like growth factor (IGF1) was mitogenic i n both perisinusoidal lipocytes and myofibroblast-like cells, respecti vely. Furthermore, whereas the expression of the mRNAs of decorin and biglycan was stimulated by TGFbeta1 in perisinusoidal lipocytes, the s ynthesis of these mRNAs was stimulated in myofibroblast-like cells pre dominantly by TGFalpha. Similar effects of TGFalpha and TGFbeta1 have been observed on the glycosaminoglycan-([S-35]sulfate incorporation) a nd proteoglycan level ([H-3]leucin incorporation into decorin and bigl ycan). 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 TGFa lpha, TGFbeta1 and PDGF depend on the cell phenotype (stage of cell ac tivation/transdifferentiation) and may be completely different in peri sinusoidal lipocytes and its transformed counterpart the myofibroblast -like cells.