Proliferation of Hepatic Oval Cells via Cyclooxygenase-2 and Extracellular Matrix Protein Signaling during Liver Regeneration Following 2-AAF/Partial Hepatectomy in Rats.
- Author:
Si Hyun BAE
1
;
Seh Hoon OH
;
Seung Kew YOON
;
Joung Ah PARK
;
Gi Dae KIM
;
Wonhee HUR
;
Jong Young CHOI
;
Il Hoan OH
;
Kun Ho YOON
Author Information
1. Department of Internal Medicine, The Catholic University of Korea, College of Medicine, Seoul, Korea. yoonsk@catholic.ac.kr
- Publication Type:Original Article
- Keywords:
Hepatic oval cells;
Cyclooxygenase-2;
Liver generation
- MeSH:
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
- From:Gut and Liver
2011;5(3):367-376
- CountryRepublic of Korea
- Language:English
-
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.
