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

Abstract

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.

The interruption of the PDGF and EGF signaling pathways by curcumin stimulates gene expression of PPARγ in rat activated hepatic stellate cell in vitro

“…38 The process of HSC activation is coupled with the sequential up-expression of receptors for growth factors, including PDGF-bR, type I & II receptors for TGF-b 39,40 and EGFR. 8 In addition, HSC activation coincides with a dramatic reduction in the abundance PPARg. [9][10][11] We previously proposed an antagonistic relationship between the activation of the signaling pathways for these growth factors and the gene expression of PPARg in HSC, that is, activation of the signaling pathways reduces the activity of PPARg by suppressing Figure 7 The blockade of the PI-3K/AKT, ERK, and/or JNK signaling pathways results in the induction of apoptosis, which is partially eliminated by the inhibition of PPARg activation.…”

“…4,[7][8][9][10][11] Prior other studies have suggested the opposite functions of PDGF and PPARg in adipogenesis. 32,33 To evaluate the effect of activation of PDGF and EGF signaling on regulation of gene expression of PPARg, exogenous PDGF and EGF were added to passaged HSC for an additional 24 h after the treatment with or without curcumin in serum-free media for 24 h. PPARg expression was determined by realtime PCR and Western blotting analyses.…”

“…It is mainly triggered by autocrine/ paracrine activation of the signaling for mitogenic plateletderived growth factor-b (PDGF) and epidermal growth factor (EGF). [3][4][5][6] The process of HSC activation is coupled with the up-expression of receptors for PDGF and EGF, 4,7,8 as well as the dramatic down-expression of peroxisome proliferatoractivated receptor-g (PPARg). [9][10][11] Both PDGF-bR and EGFR contain intrinsic tyrosine kinase activity.…”

Quantitative assessment of the effect of epidermal growth factor 61A/G polymorphism on the risk of hepatocellular carcinoma

“…EGF has been hypothesized to promote hepatocyte transformation, and dysregulation of the EGF signaling pathway has been speculated to be important in early hepatocarcinogenesis (29,30). To the best of our knowledge, numerous previously published genetic studies have demonstrated a positive association between the EGF 61A/G polymorphism and risk of HCC, while other studies have found no notable evidence that this polymorphism increases the susceptibility to HCC.…”

Pathogenesis of equine endometrosis: Relevance of the growth factors transforming growth factor- a, -b1, -b2 and -b3 and matrixmetalloproteinase-2

“…Inwieweit anderen profibrotischen Wachstumsfaktoren, wie z. B. PDGF (Pinzani et al 1996, Hoyle et al 1999, EGF (Kömüves et al 2000), CTGF (Pan et al 2001, Leask et al 2002), bFGF (Thornton et al 1992, Fibbi et al 1999) und IGF-1 (Saile et al 2004, Novosyadlyy et al 2006, die in anderen Organfibrosen nachgewiesen wurden, in der Pathogenese der equinen Endometrose eine möglicherweise größere Bedeutung zukommt, muss in nachfolgenden Studien geklärt werden.…”