After a partial hepatectomy, TGF-a mRNA has been shown of chronic liver disease; CH, chronic hepatitis; LC, liver cirrhosis; LI, labeling index; RTto increase in hepatocytes at the time of DNA synthesis con-PCR, reverse-transcriptase polymerase chain reaction; cDNA, complementary DNA.
Collagenase pretreatment and the mitogenic effects of hepatocyte growth factor and transforming growth factor-α in adult rat liver
✍ Scribed by Meng-Lun Liu; Wendy M. Mars; Reza Zarnegar; George K. Michalopoulos
- Publisher
- John Wiley and Sons
- Year
- 1994
- Tongue
- English
- Weight
- 776 KB
- Volume
- 19
- Category
- Article
- ISSN
- 0270-9139
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✦ Synopsis
Hepatocyte growth factor and transforming growth factor-a are two well-known hepatomitogens for primary hepatocyte cultures. Here we report that these two growth factors also stimulate in uiuo DNA syntheses in normal, unoperated, adult rat liver after 24-hr continuous intraportal infusion. As determined by an immunohistochemical staining technique, 5- bromo-2'-deoxyuridine incorporation was increased in a dose-dependent fashion after infusion of up to 10 pg of growth factor/100 g m body weight in the rat. Stimulation of DNA synthesis was seen in the periportal area.
Pretreatment using intraportal infusion of collagenase
(1 U/kg body weight) for 4 hr before administration of growth factor increased the labeling by 2-to 4-fold to a labeling index range of 48% to 52%. These results suggest that collagenases and possibly other proteases are involved in making hepatocytes competent to respond to growth factors at very early stages of liver regeneration. (HEPATOLOGY 1994; 19: 1521-1527.)
Hepatocyte growth factor (HGF) and transforming growth factor-alpha (TGF-a) are two well-characterized hepatomitogens for primary hepatocyte cultures. They are both reported to be primary mitogens of liver during regeneration after partial hepatectomy or administration of CCl, (1, 2). HGF is a heparin-binding heterodimeric protein with a relative molecular weight of 97 kDa. Its primary target cells are mainly of epithelial origin, including renal epithelial cells, skin keratinocytes, gastric epithelial cells, nonparenchymal epithelial liver cells and, of course, the hepatocyte (3-9). The mitogenicity of HGF in primary hepatocyte culture is 10 times more potent on a molar basis than a TGF-arelated protein, epidermal growth factor (EGF) (10). The c-met proto-oncogene product, which displays tyrosine-base activity, has been demonstrated to be the
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