PMID- 21927668 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20111110 LR - 20211020 IS - 2005-1212 (Electronic) IS - 1976-2283 (Print) IS - 1976-2283 (Linking) VI - 5 IP - 3 DP - 2011 Sep TI - Proliferation of Hepatic Oval Cells via Cyclooxygenase-2 and Extracellular Matrix Protein Signaling during Liver Regeneration Following 2-AAF/Partial Hepatectomy in Rats. PG - 367-76 LID - 10.5009/gnl.2011.5.3.367 [doi] AB - 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. FAU - Bae, Si Hyun AU - Bae SH AD - Department of Internal Medicine, The Catholic University of Korea, College of Medicine, Seoul, Korea. FAU - Oh, Seh Hoon AU - Oh SH FAU - Yoon, Seung Kew AU - Yoon SK FAU - Park, Joung Ah AU - Park JA FAU - Kim, Gi Dae AU - Kim GD FAU - Hur, Wonhee AU - Hur W FAU - Choi, Jong Young AU - Choi JY FAU - Oh, Il Hoan AU - Oh IH FAU - Yoon, Kun Ho AU - Yoon KH LA - eng PT - Journal Article DEP - 20110818 PL - Korea (South) TA - Gut Liver JT - Gut and liver JID - 101316452 PMC - PMC3166680 OTO - NOTNLM OT - Cyclooxygenase-2 OT - Hepatic oval cells OT - Liver generation COIS- No potential conflict of interest relevant to this article was reported. EDAT- 2011/09/20 06:00 MHDA- 2011/09/20 06:01 PMCR- 2011/09/01 CRDT- 2011/09/20 06:00 PHST- 2010/12/10 00:00 [received] PHST- 2011/04/27 00:00 [accepted] PHST- 2011/09/20 06:00 [entrez] PHST- 2011/09/20 06:00 [pubmed] PHST- 2011/09/20 06:01 [medline] PHST- 2011/09/01 00:00 [pmc-release] AID - 10.5009/gnl.2011.5.3.367 [doi] PST - ppublish SO - Gut Liver. 2011 Sep;5(3):367-76. doi: 10.5009/gnl.2011.5.3.367. Epub 2011 Aug 18.