Hepatic COX-2 overexpression is sufficient to induce hepatitis, but its role on liver fibrosis remains unknown. We aim to elucidate possible biological effects of COX-2 in liver fibrosis using both gain-of-function and loss-of-function mouse models. COX-2 transgenic (TG) mice that specificall
y overexpress the human COX-2 cDNA in the liver, knockout (KO), and wild t
ype (WT) mice were studied in two different murine fibrosis models induced b
y carbon tetrachloride (CCl
4) injection or methionine and choline-deficient (MCD) diet. Liver injur
y was assessed b
y serum ALT and bilirubin levels and histological examination. Hepatic collagen content was determined b
y picrosirius red stain morphometr
y assa
y and quantitation of h
ydrox
yproline. Hepatic stellate cell (HSC) activation was determined b
y immunohistochemical anal
ysis of
-smooth muscle actin (
-SMA). mRNA expression of fibrogenic genes was assa
yed b
y real-time quantitative PCR. COX-2 protein was overexpressed in the liver of TG mice compared with WT littermates. CCl
4 or MCD-induced liver fibrotic injur
y was equall
y severe in TG and WT mice, as demonstrated b
y similar elevated levels of hepatic collagen contents. Enhanced COX-2 expression in TG liver did not affect HSC activation and fibrogenic gene expression upon CCl
4 or MCD treatment. Importantl
y, CCl
4-treated KO mice did not show significant difference in liver fibrotic damage and fibrogenic gene expression compared with the WT counterparts. This is the first report on the effect of COX-2 in liver fibrosis based on genetic mouse models. The results suggest that COX-2 does not appear to mediate the development of liver fibrosis.