Role of transforming growth factor beta 1 on hepatic regeneration and apoptosis in liver diseases.
Open Access
- 1 December 1995
- journal article
- research article
- Published by BMJ in Journal of Clinical Pathology
- Vol. 48 (12), 1093-1097
- https://doi.org/10.1136/jcp.48.12.1093
Abstract
AIMS--To investigate the effects of transforming growth factor beta 1 (TGF-beta 1) on regeneration and induction of apoptosis of liver cell and bile duct in various liver diseases. METHODS--Formalin fixed paraffin wax sections of 18 liver tissue samples were obtained by needle biopsy, surgery, or necropsy; these included six liver cirrhosis, three obstructive jaundice; five fulminant hepatitis, one subacute hepatitis, and three normal liver. Expression of TGF-beta 1, apoptosis related Le(y) antigen, Fas antigen, a receptor for tumour necrosis factor, and biotin nick end labelling with terminal deoxynucleotidyl transferase mediated dUTP (TUNEL) for locating DNA fragmentation, was investigated histochemically. RESULTS--TGF-beta 1 was expressed in areas of atypical bile duct proliferation, where bile duct continuously proliferated from liver cells. In occlusive jaundice and fulminant hepatitis, TUNEL was positive in nuclei and cytoplasm of metaplastic cells which formed incomplete bile ducts, and these cells appeared to extend from TGF-beta 1 expressing liver cells. Fas antigen was found only on the cell membrane of proliferated bile duct in fulminant hepatitis, which differed from TGF-beta 1 and TUNEL positive areas. Le(y) antigen was expressed in liver cell and bile duct at the areas with atypical bile duct proliferation, but its coexpression with TUNEL was rare. CONCLUSIONS--TGF-beta 1 plays a role in the arrest of liver cell regeneration and atypical bile duct proliferation, and in areas of rapidly progressing atypical bile duct proliferation, such as in fulminant hepatitis or bile retention. Apoptosis appears to be induced by TGF-beta 1. This phenomenon may account for the inadequate hepatic regeneration that occurs with liver disease.Keywords
This publication has 41 references indexed in Scilit:
- Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation.The Journal of cell biology, 1992
- Increased transforming growth factor-β1 gene expression in human liver diseaseJournal of Hepatology, 1992
- Transforming Growth Factors β1 and α in Chronic Liver DiseaseNew England Journal of Medicine, 1991
- The Transforming Growth Factor-beta FamilyAnnual Review of Cell Biology, 1990
- Origin and involution of hyperplastic bile ductules following total biliary obstructionLiver International, 1990
- Interleukin-1β is a potent growth inhibitor of adult rat hepatocytes in primary cultureExperimental Cell Research, 1988
- Type beta transforming growth factor reversibly inhibits the early proliferative response to partial hepatectomy in the rat.Proceedings of the National Academy of Sciences, 1988
- Immunohistochemical study on bile ductular proliferation in various hepatobiliary diseasesLiver International, 1986
- Deletion of hyperplastic biliary epithelial cells by apoptosis following removal of the proliferative stimulusLiver International, 1985
- Ultrastructural changes in the bile canaliculi and the lateral surfaces of rat hepatocytes during restorative proliferationVirchows Archiv B Cell Pathology Including Molecular Pathology, 1982