BACKGROUND: Transforming growth factor beta (TGF-beta) regulates hepatocyte proliferation and biosynthesis of the extracellular matrix. AIMS: 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.
BACKGROUND: Transforming growth factor beta (TGF-beta) regulates hepatocyte proliferation and biosynthesis of the extracellular matrix. AIMS: 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.
Authors: G Ramadori; T Knittel; M Odenthal; S Schwögler; K Neubauer; K H Meyer zum Büschenfelde Journal: Gastroenterology Date: 1992-10 Impact factor: 22.682
Authors: S Sanz; J B Pucilowska; S Liu; C M Rodríguez-Ortigosa; P K Lund; D A Brenner; C R Fuller; J G Simmons; A Pardo; M-L Martínez-Chantar; J A Fagin; J Prieto Journal: Gut Date: 2005-01 Impact factor: 23.059