Gut Liver.  2011 Sep;5(3):367-376.

Proliferation of Hepatic Oval Cells via Cyclooxygenase-2 and Extracellular Matrix Protein Signaling during Liver Regeneration Following 2-AAF/Partial Hepatectomy in Rats

• Bae SH
• Oh SH
• Yoon SK
• Park JA
• Kim GD
• Hur W
• Choi JY
• Oh IH
• Yoon KH

Abstract

BACKGROUND/AIMS
In the 2-acetylaminofluorene (2-AAF)/70% partial hepatectomy (PHx) model, the mechanism underlying the differentiation of activated hepatic oval cells (HOCs) into hepatocytes and bile ductile cells is unclear. We investigated the role of cyclooxygenase-2 (COX-2) in HOCs and the relationship between COX-2 and extracellular matrix proteins in cellular proliferation.
METHODS
Reverse transcription-polymerase chain reaction, immunohistochemical staining, and Western blotting were used to assess COX-2 expression. The co-localization of COX-2 with Thy1, c-Met, epithelial cell adhesion molecule, and alpha-smooth muscle actin was also examined. Additionally, we investigated whether connective tissue growth factor (CTGF), fibronectin (FN), extracellular signal-regulated kinase 1/2 (P-ERK1/2), and AKT were expressed in HOCs.
RESULTS
The expression of COX-2, prostaglandin E2 receptors, and c-Met was upregulated in HOCs. However, HOCs treated with the COX-2 inhibitor NS398 showed decreased COX-2, CTGF, FN, and AKT expression, whereas P-ERK1/2 was unaffected. Additionally, NS398 inhibited HOC proliferation, but not the proliferation of HOCs cultured on FN-coated dishes. Furthermore, the proliferative response of HOCs treated with NS398 was reversed by hepatic growth factor treatment.
CONCLUSIONS
These results suggest that HOC proliferation is mediated through COX-2, extracellular FN expression, and AKT activation. Thus, COX-2 plays an important role in HOC proliferation following acute injury.

Keyword

Hepatic oval cells; Cyclooxygenase-2; Liver generation

MeSH Terms

2-Acetylaminofluorene
Actins
Animals
Antigens, Neoplasm
Bile
Blotting, Western
Cell Adhesion Molecules
Connective Tissue Growth Factor
Cyclooxygenase 2
Dinoprostone
Epithelial Cells
Extracellular Matrix
Extracellular Matrix Proteins
Fibronectins
Hepatectomy
Hepatocytes
Liver
Liver Regeneration
Muscles
Nitrobenzenes
Phosphotransferases
Rats
Sulfonamides
2-Acetylaminofluorene
Actins
Antigens, Neoplasm
Cell Adhesion Molecules
Connective Tissue Growth Factor
Cyclooxygenase 2
Dinoprostone
Extracellular Matrix Proteins
Fibronectins
Nitrobenzenes
Phosphotransferases
Sulfonamides