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Tumor necrosis factor alpha (TNFα) and transforming growth factor β1 (TGFβ1) stimulate fibronectin synthesis and the transdifferentiation of fat-storing cells in the rat liver into myofibroblasts

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Virchows Archiv B

Summary

Transforming growth factor-β (TGFβ1) and tumor necrosis factor alpha (TNFα) stimulate the trans-differentiation of fat-storing cells (FSC) in the rat liver into highly active and “synthetic” myofibroblast-like cells (MFBIC). This activation has been documented by differential-interference contrast and light microscopy using morphologic criteria (a reduction in the number and size of fat droplets, cell flattening and the development of long cytoplasmic extensions), by the loss of retinyl-palmitate (measured by HPLC) and by the enhanced expression of iso-α smooth muscle actin (demonstrated by immunofluorescence microscopy). Furthermore, while cell growth measured by the cell count and DNA content is slightly inhibited by TGFβ1 (0.81 of the control), the combination of TGFβ1 with TNFα stimulates cell proliferation to 1.44 times of the control. In addition the combination of TGFβ and TNFα potentiated the stimulatory effect on fibronectin synthesis (TGFβ alone: 1.4 times control; TNFα alone: 2.2 times control; TGFβ plus TNFα: 4.7 times control). The total protein synthesis was not altered by TGFβ or TNFα. In summary the results obtained identify TGFβ and TNFα as mediators stimulating key events in liver fibrogenesis (i.e. FSC proliferation, FSC transdifferentiation into MFBIC, and fibronectin synthesis).

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Authors and Affiliations

  1. Department of Clinical Chemistry and Central Laboratory, Philipps-University, W-3550, Marburg, Germany

    Max G. Bachem, Klaus-Martin Sell, Ralf Melchior, Jürgen Kropf, Thomas Eller & Axel M. Gressner

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  1. Max G. Bachem
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  2. Klaus-Martin Sell
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  3. Ralf Melchior
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Bachem, M.G., Sell, KM., Melchior, R. et al. Tumor necrosis factor alpha (TNFα) and transforming growth factor β1 (TGFβ1) stimulate fibronectin synthesis and the transdifferentiation of fat-storing cells in the rat liver into myofibroblasts. Virchows Archiv B Cell Pathol 63, 123–130 (1993). https://doi.org/10.1007/BF02899251

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