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Journal of Histochemistry and Cytochemistry, Vol. 48, 821-830, June 2000, Copyright © 2000, The Histochemical Society, Inc.

ARTICLE

Expression of Epidermal Growth Factor and Its Receptor in Cirrhotic Liver Disease

László G. Kömüvesa, Anna Ferenc, Albert L. Jonesb,c,d, and Eric Fodorc,d
a Departments of Dermatology, University of California–San Francisco
b Anatomy, and Medicine, University of California–San Francisco
c Department of Cell Biology, Veterans Affairs Medical Center–San Francisco
d Liver Center, University of California–San Francisco, San Francisco, California

Correspondence to: László G. Kömüves, COR Therapeutics, Inc., 256 E. Grand Ave., So. San Francisco, CA 94080. E-mail: lkomuves@corr.com

Polypeptide growth factors, including epidermal growth factor (EGF), play a central role in regulating hepatocyte growth both in vivo and in primary culture. To characterize EGF gene expression in the pathogenesis of regenerative cirrhotic fibrosis, we employed biotinylated antisense oligonucleotide probes to localize hepatic mRNA transcripts in situ. In control tissue and regenerative hepatic nodules, EGF receptor (EGFR) mRNA transcripts were expressed constitutively. In contrast, oligonucleotide probes targeting the human EGF coding region showed that EGF transcription was extremely low in control liver but was highly elevated and localized to regenerative hepatic nodules and bile duct epithelia of cirrhotic liver. To determine whether EGF mRNA accumulation accompanied a comparable increase in the EGF peptide, we performed immunohistochemistry using an antibody specific for the nonprocessed peptide aminoterminus. We observed that positive localized EGF staining paralleled its mRNA transcript. These results indicate that EGF upregulation is a characteristic of cirrhotic liver disease and suggest that persistent de novo ligand synthesis and its signaling contribute to an autocrine-mediated hepatocyte proliferation within the regenerative nodule. (J Histochem Cytochem 48:821–830, 2000)

Key Words: EGF, EGF receptor, liver cirrhosis, hepatocytes


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