Induction of rat liver parenchymal cell apoptosis by hepatic myofibroblasts via transforming growth factor β

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Abstract
The induction of apoptosis of rat liver parenchymal cells (PC) by transforming growth factor β (TGF-β)-expressing transforming fat-storing cells (FSC), i.e., myofibroblasts (MFB), was studied under culture conditions and compared with the apoptotic effect of human recombinant TGF-β1. MFB were obtained by subculture of FSC. The TGF-β concentration in the conditioned medium of myofibroblast (MFBcM) determined with the Mink cell proliferation inhibition assay was 1. The exclusive role of active TGF-β in MFBcM as mediator of the apoptotic effects of MFB was proven by preincubation of the conditioned medium with human recombinant latency-associated peptide, which reversed completely MFBcM induced reduction of the XTT-test and the MFBcM-generated increase of oligonucleosomal DNA fragments. Partial reversibility was reached by preincubation of the medium with recombinant soluble type II TGF-β receptor. The data let us conclude that transformed FSC, i.e., MFB in damaged liver, could participate in the mechanisms of PC apoptosis by paracrine loops involving TGF-β.

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