Modulation of transforming growth factor beta function in hepatocytes and hepatic stellate cells in rat liver injury.
BACKGROUND
Transforming growth factor beta (TGF-beta) regulates hepatocyte proliferation and biosynthesis of the extracellular matrix.


OBJECTIVE
This study investigated alternations in sensitivity to TGF-beta1 and binding properties for ligand in hepatocytes and hepatic stellate cells (HSC) after CCl(4) administration.


METHODS
Plasma TGF-beta1 levels in rats after CCl(4) administration were determined using ELISA. Effects of TGF-beta1 were examined by DNA synthesis in hepatocytes and by measurement of fibronectin production in HSC after CCl(4) administration. Binding of (125)I TGF-beta1 was tested in these cells.


RESULTS
Plasma TGF-beta1 levels were increased as early as 24 hours and were maximal by 48 hours. The antiproliferative response to TGF-beta1 decreased in hepatocytes at 48 hours and normalised at 72 hours. Fibronectin production of both normal and injured HSC was affected by TGF-beta1 treatment. Cross linked ligand/receptor complexes were detected in normal hepatocytes and HSC. However, these levels decreased specifically in hepatocytes at 48 hours and normalised by 72 hours.


CONCLUSIONS
Downregulation of TGF-beta receptor occurred in hepatocytes after chemical insult and TGF-beta1 could not transduce its antiproliferative signal. Recovery of TGF-beta receptor expression causes the signal to transduce to the nucleus at 72 hours. In HSC, whenever TGF-beta1 is increased, TGF-beta1 can transduce its signal for fibronectin production via its receptor because signalling receptors are expressed constantly.
Date
M
M
Third Department of Internal Medicine, Kansai Medical University, 10-15 Fumizonocho, Moriguchi, Osaka 570-8507, Japan.
Matsuzaki
K
K
Matsushita
M
M
Tahashi
Y
Y
Furukawa
F
F
Inoue
K
K
D000818:Animals; D002251:Carbon Tetrachloride; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D005353:Fibronectins / Q000096:biosynthesis; D007457:Iodine Radioisotopes / Q000378:metabolism; D008099:Liver / Q000502:physiology*; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D012333:RNA, Messenger / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D018125:Receptors, Transforming Growth Factor beta / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000097:blood / Q000494:pharmacology / Q000502:physiology*
D005353:Fibronectins; D007457:Iodine Radioisotopes; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D004247:DNA; D002251:Carbon Tetrachloride