Transforming growth factor-α expression during liver regeneration after partial hepatectomy and toxic injury, and potential interactions between transforming growth factor-α and hepatocyte growth factor

✍ Scribed by Eric M. Webber; Mark J. Fitzgerald; Pamela I. Brown; Molly H. Bartlett; Nelson Fausto

• Publisher: John Wiley and Sons
• Year: 1993
• Tongue: English
• Weight: 995 KB
• Volume: 18
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840180622

✦ Synopsis

Transforming growth factor-a and hepatocyte growth factor are important stimulators of hepatocyte proliferation. In this series of experiments we sought to measure the expression of transforming growth factor-a mRNA by hepatocytes in response to toxic liver injury produced by carbon tetrachloride or galactosamine and to perform a more detailed analysis of transforming growth factor-a expression after partial hepatectomy. We also explored the interactions of transforming growth factor-u and hepatocyte growth factor in their effects on hepatocytes in vitro and tested the ability of these factors to stimulate endog enous transforming growth factor-a production by hepatocytes. In previous work we have used oligonucleotide probes to measure transforming growth factor-a mRNA expression after partial hepatectomy. In this study we used a rat transforming growth factor-a cDNA probe and found that the level of liver transforming growth factor-a mRNA increases 4 hr after partial hepatectomy, shows peak expression at 18 hr and returns to the normal level by 36 to 48 hr. Measurement of the corresponding peptide in the liver by means of radioimmunoassay shows that the level of transforming growth factor-a rises by 12 hr, peaks at 24 hr and remains significantly increased at 48 hr compared with the levels in sham-operated rats. Carbon tetrachloride and galactosamine are known to produce different patterns of acute liver injury, with maximal hepatocyte DNA synthesis at 48 hr and 5 days, respectively. After carbon tetrachloride administration the profiles of the transforming growth factor-a and hepatocyte growth factor mRNA expression are similar, each showing two peaks. the first at 12 hr and the