Tumor necrosis factor alpha (TNF alpha) and transforming growth factor beta 1 (TGF beta 1) stimulate fibronectin synthesis and the transdifferentiation of fat-storing cells in the rat liver into myofibroblasts.
Transforming growth factor-beta (TGF beta 1) and tumor necrosis factor alpha (TNF alpha) stimulate the transdifferentiation 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-alpha smooth muscle actin (demonstrated by immunofluorescence microscopy). Furthermore, while cell growth measured by the cell count and DNA content is slightly inhibited by TGF beta 1 (0.81 of the control), the combination of TGF beta 1 with TNF alpha stimulates cell proliferation to 1.44 times of the control. In addition the combination of TGF beta and TNF alpha potentiated the stimulatory effect on fibronectin synthesis (TGF beta alone: 1.4 times control; TNF alpha alone: 2.2 times control; TGF beta plus TNF alpha: 4.7 times control). The total protein synthesis was not altered by TGF beta or TNF alpha. In summary the results obtained identify TGF beta and TNF alpha as mediators stimulating key events in liver fibrogenesis (i.e. FSC proliferation, FSC transdifferentiation into MFBIC, and fibronectin synthesis).
Bachem
M G
MG
Department of Clinical Chemistry, Philipps-University, Marburg, Germany.
Sell
K M
KM
Melchior
R
R
Kropf
J
J
Eller
T
T
Gressner
A M
AM
D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects*; D000818:Animals; D002452:Cell Count / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects*; D005353:Fibronectins / Q000096:biosynthesis*; D008099:Liver / Q000737:chemistry / Q000166:cytology / Q000187:drug effects*; D008854:Microscopy, Electron; D014176:Protein Biosynthesis; D051381:Rats; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D005353:Fibronectins; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D004247:DNA