Cytoplasmic domain of tissue factor promotes liver fibrosis in mice

Figure 1 Hepatic fibrosis area. Wildtype control mice administered vehicle alone showed minimal fibrosis (A). Compared to CCl₄ treated wild-type mice (B), hepatic fibrosis area was significantly lower in the PAR-2^-/- (C), TF^§CT/§CT (D) and TF^§CT/§CT/PAR-2^-/- (E) mice after CCl₄ exposure for 8 wk. (^bP < 0.01, ^cP < 0.001 ^dP < 0.0001).

Figure 2 Hepatic hydroxyproline content. Hydroxyproline content, a surrogate marker for collagen, was significantly less in the PAR-2^-/-, TF^§CT/§CT and TF^§CT/§CT-PAR-2 KO mice compared to wildtype mice (^aP < 0.05).

Figure 3 Hepatic stellate cell activation (smooth muscle actin expression). The number of αSMA positive cells was significantly lower in the TF^§CT/§CT and TF^§CT/§CT/PAR-2^-/- mice compared to wildtype and was similar to PAR-2 KO mice (^bP < 0.01, ^dP < 0.0001).

Figure 4 TGFβ mRNA and protein expression. A: TGFβ mRNA expression was significantly lower in the TF§^CT/§CT group with a similar but non-significant trend in TF^§CT/§CT/PAR-2^-/- mice compared to wildtype. Levels were similar to PAR-2 KO mice, which were also significantly lower than WT; B: TGFβ protein was significantly lower in TF^§CT/§CT, TF^§CT/§CT/PAR-2^-/- and PAR-2^-/- mice compared to wildtype with levels similar to vehicle controls. ^cP < 0.001, ^dP < 0.0001. ns: Not significant.

Figure 5 Matrix metalloproteinase expression. MMP-2 mRNA expression was significantly lower in TF^§CT/§CT, TF^{§CT/ §CT}/PAR-2^-/- and PAR-2^-/- mice compared to wildtype. ^bP < 0.01, ^cP < 0.001, ^dP < 0.0001.

Figure 6 Hepatic macrophage expression. There were significantly fewer activated CD68⁺ macrophages in both TF^§CT/§CT and TF^§CT/§CT/PAR-2^-/- mice compared with WT mice. ^aP < 0.05, ^cP < 0.001.