Transforming growth factor-beta gene expression in normal and fibrotic rat liver - PubMed (original) (raw)
Transforming growth factor-beta gene expression in normal and fibrotic rat liver
P J De Bleser et al. J Hepatol. 1997 Apr.
Abstract
Background/aims: Transforming growth factor-beta (TGF-beta) is considered to be an important mediator in the development of fibrosis in several chronic liver diseases. To understand the mechanism(s) by which TGF-beta exerts its action(s), we investigated the cellular distribution of TGF-beta(1,2,3) transcripts in normal and carbon tetrachloride (CCl4)-induced fibrotic rat liver.
Methods: Parenchymal, sinusoidal endothelial, Kupffer and stellate cells were isolated and purified. The exact cellular composition of each isolate was determined by transmission electron microscopy. Expression of TGF-beta(1,2,3) transcripts was investigated using Northern hybridization analysis. Hybridization signals were quantified by scanning densitometry and corrected for: (i) differences in extractable RNA per cell type, (ii) signal contribution from contaminating cells, and (iii) differences in loading, capillary transfer and hybridization.
Results: In normal liver, TGF-beta1 mRNA was predominantly expressed in Kupffer cells, exhibiting values approximately 9-fold higher than those in stellate cells. No expression was found in endothelial and parenchymal cells. Signals for TGF-beta2 and TGF-beta3 were much weaker when compared to TGF-beta1. In Kupffer cells, the level of TGF-beta2 was approximately 4-fold higher than in stellate cells. Little expression was found in endothelial cells. TGF-beta3 expression could only be detected in stellate cells. TGF-beta2 and TGF-beta3 was not expressed in parenchymal cells. In fibrotic liver, TGF-beta1 mRNA was strongly expressed in all the sinusoidal cells. TGF-beta2 and TGF-beta3 could no longer be detected. When compared to the level of expression in normal stellate cells, the level of TGF-beta1 increased 12-fold in stellate cells from fibrotic livers, and 6-fold in endothelial cells. In Kupffer cells, the level of expression remained unchanged.
Conclusions: (i) In both normal and fibrotic liver, TGF-beta1 is the most abundant isoform, (ii) in normal liver, TGF-beta1 is expressed strongly by Kupffer cells and moderately by stellate cells, TGF-beta2 expression is highest in Kupffer cells, followed by stellate cells and endothelial cells. TGF-beta3 is expressed by stellate cells, (iii) in fibrotic liver, the level of TGF-beta1 expression increases selectively in stellate cells and endothelial cells. This suggests an important role, not only for stellate, but also for endothelial cells in fibrogenesis.
Similar articles
- Increased expression of plasminogen activator and plasminogen activator inhibitor during liver fibrogenesis of rats: role of stellate cells.
Zhang LP, Takahara T, Yata Y, Furui K, Jin B, Kawada N, Watanabe A. Zhang LP, et al. J Hepatol. 1999 Oct;31(4):703-11. doi: 10.1016/s0168-8278(99)80351-1. J Hepatol. 1999. PMID: 10551395 - Cooperation of liver cells in health and disease.
Kmieć Z. Kmieć Z. Adv Anat Embryol Cell Biol. 2001;161:III-XIII, 1-151. doi: 10.1007/978-3-642-56553-3. Adv Anat Embryol Cell Biol. 2001. PMID: 11729749 Review. - Experimental and human liver fibrogenesis.
Kovalszky I, Nagy P, Szende B, Lapis K, Szalay F, Jeney A, Schaff Z. Kovalszky I, et al. Scand J Gastroenterol Suppl. 1998;228:51-5. doi: 10.1080/003655298750026561. Scand J Gastroenterol Suppl. 1998. PMID: 9867113 Review.
Cited by
- Serum transforming growth factor beta 3 predicts future development of nonalcoholic fatty liver disease.
Wei Y, Tian Q, Zhao X, Wang X. Wei Y, et al. Int J Clin Exp Med. 2015 Mar 15;8(3):4545-50. eCollection 2015. Int J Clin Exp Med. 2015. PMID: 26064382 Free PMC article. - Effects of retinoic acid on proliferation, phenotype and expression of cyclin-dependent kinase inhibitors in TGF-beta1-stimulated rat hepatic stellate cells.
Huang GC, Zhang JS, Zhang YE. Huang GC, et al. World J Gastroenterol. 2000 Dec;6(6):819-823. doi: 10.3748/wjg.v6.i6.819. World J Gastroenterol. 2000. PMID: 11819702 Free PMC article. - TGF-β1 and TGF-β2 abundance in liver diseases of mice and men.
Dropmann A, Dediulia T, Breitkopf-Heinlein K, Korhonen H, Janicot M, Weber SN, Thomas M, Piiper A, Bertran E, Fabregat I, Abshagen K, Hess J, Angel P, Coulouarn C, Dooley S, Meindl-Beinker NM. Dropmann A, et al. Oncotarget. 2016 Apr 12;7(15):19499-518. doi: 10.18632/oncotarget.6967. Oncotarget. 2016. PMID: 26799667 Free PMC article. - Hepatic stellate cells: protean, multifunctional, and enigmatic cells of the liver.
Friedman SL. Friedman SL. Physiol Rev. 2008 Jan;88(1):125-72. doi: 10.1152/physrev.00013.2007. Physiol Rev. 2008. PMID: 18195085 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources