title: Proliferation of Hepatic Oval Cells via Cyclooxygenase-2 and Extracellular Matrix Protein Signaling during Liver Regeneration Following 2-AAF/Partial Hepatectomy in Rats.
abstract: OBJECTIVE
  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 α-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.
authors.affiliation: Department of Internal Medicine, The Catholic University of Korea, College of Medicine, Seoul, Korea.
authors.forename: Si Hyun
authors.initials: SH
authors.lastname: Bae
authors.forename: Seh Hoon
authors.initials: SH
authors.lastname: Oh
authors.forename: Seung Kew
authors.initials: SK
authors.lastname: Yoon
authors.forename: Joung Ah
authors.initials: JA
authors.lastname: Park
authors.forename: Gi Dae
authors.initials: GD
authors.lastname: Kim
authors.forename: Wonhee
authors.initials: W
authors.lastname: Hur
authors.forename: Jong Young
authors.initials: JY
authors.lastname: Choi
authors.forename: Il Hoan
authors.initials: IH
authors.lastname: Oh
authors.forename: Kun Ho
authors.initials: KH
authors.lastname: Yoon