Proliferation of Hepatic Oval Cells via Cyclooxygenase-2 and Extracellular Matrix Protein Signaling during Liver Regeneration Following 2-AAF/Partial Hepatectomy in Rats
Gut and Liver
;
: 367-376, 2011.
Article
in English
| WPRIM
| ID: wpr-205657
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Phosphotransferases
/
2-Acetylaminofluorene
/
Sulfonamides
/
Bile
/
Dinoprostone
/
Cell Adhesion Molecules
/
Blotting, Western
/
Extracellular Matrix Proteins
/
Actins
/
Fibronectins
Type of study:
Prognostic study
Limits:
Animals
Language:
English
Journal:
Gut and Liver
Year:
2011
Type:
Article
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