Hypoxia potentiates transforming growth factor-β expression of hepatocyte during the cirrhotic condition in rat liver
Article first published online: 26 NOV 2004
Volume 24, Issue 6, pages 658–668, December 2004
How to Cite
Jeong, W.-I., Do, S.-H., Yun, H.-S., Song, B.-J., Kim, S.-J., Kwak, W.-J., Yoo, S.-E., Park, H.-Y. and Jeong, K.-S. (2004), Hypoxia potentiates transforming growth factor-β expression of hepatocyte during the cirrhotic condition in rat liver. Liver International, 24: 658–668. doi: 10.1111/j.1478-3231.2004.0961.x
- Issue published online: 26 NOV 2004
- Article first published online: 26 NOV 2004
- Received 15 January 2004, accepted 01 June 2004
- smad protein;
- transforming growth factor beta
Abstract: Background/Aims: Many studies have reported that hypoxia might be associated with angiogenesis and fibrogenesis, and the level of transforming growth factor-β1 (TGF-β1) was increased in fibrotic liver and maximal at cirrhosis. Therefore, we examined the expression of TGF-β1, phosphorylated-Smad2/3 (p-Smad2/3) of the TGF-β immediate down stream signaling system and hypoxic status during hepatic fibrogenesis.
Methods: Fibrosis of rats was induced by carbon tetrachloride. Collagens were detected with Azan stain. Immunohistochemistry and immunoblotting was used.
Results: TGF-β1 was mainly produced by hypoxic hepatocytes at cirrhosis although myofibroblasts (MFBs) and macrophages producing TGF-β1 were decreased. Moreover, distribution of p-Smad2/3 in hepatocytes was consistent with those of hypoxic hepatocytes regardless of MFBs. Furthermore, in recovery, most MFBs disappeared, whereas positive reactions of p-Smad2/3 still existed in the hepatocytes of hypoxic areas. Therefore, TGF-β1 expression in hepatocytes might have been associated with hypoxia.
Conclusions: We put forward the hypothesis that TGF-β1 is mainly produced by MFBs and macrophages at early and middle stages of fibrotic processes, but it is predominantly released by hypoxic hepatocytes in the last fibrotic stage or cirrhosis.