Abstract

BACKGROUND Transforming growth factor β (TGF-β) regulates hepatocyte proliferation and biosynthesis of the extracellular matrix.

AIMS This study investigated alternations in sensitivity to TGF-β1 and binding properties for ligand in hepatocytes and hepatic stellate cells (HSC) after CCl₄ administration.

METHODS Plasma TGF-β1 levels in rats after CCl₄ administration were determined using ELISA. Effects of TGF-β1 were examined by DNA synthesis in hepatocytes and by measurement of fibronectin production in HSC after CCl₄ administration. Binding of¹²⁵I TGF-β1 was tested in these cells.

RESULTS Plasma TGF-β1 levels were increased as early as 24 hours and were maximal by 48 hours . The antiproliferative response to TGF-β1 decreased in hepatocytes at 48 hours and normalised at 72 hours. Fibronectin production of both normal and injured HSC was affected by TGF-β1 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-β receptor occurred in hepatocytes after chemical insult and TGF-β1 could not transduce its antiproliferative signal. Recovery of TGF-β receptor expression causes the signal to transduce to the nucleus at 72 hours. In HSC, whenever TGF-β1 is increased, TGF-β1 can transduce its signal for fibronectin production via its receptor because signalling receptors are expressed constantly.