Abstract: Objective To evaluate the feasibility of uPA knock-out (uPA^-/-) mice liver fibrosis model by analysing the expression of α-Smooth Muscle Actin (α-SMA) and Matrix Metalloproteinase-13 (MMP13). Methods Adult male C57BL/6J WT mice and uPA knock-out (uPA^-/-) mice were divided into four groups with 10 mice in each group: control groups (Con-WT, Con- uPA^-/-) and liver fibrosis model groups (Mod-WT, Mod-uPA^-/-). Mice were intraperitoneally injected with 0.15ml 10% CCl₄ (or olive oil as control) twice per week for 6 weeks to induce liver fibrosis. The mRNA expression of á-SMA and MMP13 was detected by real-time polymerase chain reaction (PCR) and the protein expression of α-SMA and MMP13 was analyzed by western blot and immunohistochemistry. Result The real-time PCR showed that the mRNA expression of α-SMA, MMP13 in uPA^-/- mice wes significantly higher than that in WT mice. The western blot results indicated that there were no expression of α-SMA protein and MMP13 protein of the mice liver in the control group, a few expression of α-SMA protein in Mod-WT group, and a significant increase of α-SMA protein expression in the Mod-uPA^-/- group. The immunohistochemistry results demonstrated that the protein expression of α-SMA and MMP13 of Mod-uPA^-/- group was higher than Mod-WT group. Conclusion The mRNA and protein expression of α-SMA were significantly higher in the uPA^-/- mice. The knocking-out of the uPA gene promoted the hepatic stellate cells transforming into myofibroblasts, thus speeding up the deposition of extracellular matrixin in the liver. Also, the protein expression of MMP13 in liver fibrosis model mice was significantly increased. uPA^-/- mice are susceptible animal strain to establish liver fibrosis model.

Key words: uPA knock-out mice, Liver fibrosis, α-SMA, MMP13