Gastroenterology

Gastroenterology

Volume 123, Issue 6, December 2002, Pages 2017-2027
Gastroenterology

Basic–Liver, Pancreas, and Biliary Tract
Diverse expression of ErbB receptor proteins during rat liver development and regeneration,☆☆

https://doi.org/10.1053/gast.2002.37060Get rights and content

Abstract

Background & Aims: The protein expression and interactions of the ErbB receptors were examined in different liver proliferation models in vivo and in vitro, including ontogeny and regeneration following partial hepatectomy. Methods: Expression and tyrosine phosphorylation status of specific ErbB proteins were studied by immunologic methods. Results: The epidermal growth factor receptor, ErbB2, and ErbB3 were the only ErbB proteins detected in the liver parenchyma on embryonic day 19. ErbB2 disappeared by the third week after birth and could not be appreciably induced in the adult animal by partial hepatectomy. ErbB2 was also detected in multipotent stem (RLE) and hepatoma (H4IIe) cell lines as well as in fetal, but not adult, hepatocyte cultures. Only epidermal growth factor receptor and ErbB3 were detected in adult liver, and both showed circadian variation in protein expression. ErbB4 was not detected in any model. Patterns of ligand-induced ErbB phosphorylation differed between fetal and adult hepatocytes. Conclusions: Complex and independent programs regulate the ErbB receptors, with implications for differential cell signaling in hepatic development and regeneration.

GASTROENTEROLOGY 2002;123:2017-2027

Section snippets

Animals

Male Sprague–Dawley rats (150–200 g) from Harlan (Indianapolis, IN) were housed under conditions of regulated lighting (lights on from 6 AM to 6 PM) and ad libitum access to water and Purina rodent chow (Ralston-Purina, St. Louis, MO). For the developmental study, timed pregnant female rats were obtained from Harlan and rat pups harvested surgically or postpartum. All protocols used were approved in advance by the Animal Use Subcommittee of the Vanderbilt Animal Care Committee.

Partial

ErbB receptor expression during liver development

To evaluate ErbB protein expression in hepatic development, ErbB proteins were immunoprecipitated from liver lysates (800 μg) and then immunoblotted with the immunoprecipitating antibodies. Immunoprecipitates were prepared from whole rat embryos at E16, embryonic rat liver at E19, neonatal liver (~24 hours after birth), and 1, 2, and 3 weeks postpartum liver using Western analysis. Bands corresponding to the 170- to 185-kilodalton forms of ErbB1, ErbB2, and ErbB3 were detected at various

Discussion

Examination of the expression levels of hepatic ErbB receptors in embryonic, neonatal weanling, and adult rats showed that EGF-R, ErbB2, and ErbB3 are differentially expressed during the development of rat liver (Figure 1). As suggested by the normal liver development in EGF-R/null25, 26 and kinase-impaired wa-2 mice,27 EGF-R signaling does not seem to be required for hepatic organogenesis. EGF binding and EGF-dependent kinase activity have previously been shown to be absent from the liver

Acknowledgements

The authors thank Dr. Arnold Strauss for support and encouragement, Silvio Sitaric for technical assistance, Dr. David Threadgill for critical review of this manuscript, and Dr. Snorri Thorgeirsson for providing us with the RLE cell line.

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    Supported by National Institutes of Health grant DK 53804 (to W.E.R.).

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