Figure 1.

Endothelial VCAM1 promotes LSEC capillarization during liver injury. Eight-week-old WT C57BL/6J mice were fed either chow or FFC diet for 24 weeks to induce NASH and treated with either anti-VCAM1Ab or control IgG isotype Ab (IgG) twice a week for the last 4 weeks. (A) Schematic representation of the experimental mouse study. (B) Hepatic mRNA expression of Cd34 was assessed by real-time PCR. Fold change was determined after normalization to 18s rRNA and expressed relative to chow-IgG mice. n=5-7. (C) Representative images of Lyve1 immunostaining of liver sections (left). Scale bar: 100 μm. Lyve1 positive areas were quantified in 10 random 10x microscopic fields and averaged for each animal (right). n=4-7. Vcam1^fl/fl and Vcam1^Δend mice were fed the CD-HFD diet starting at the age of 8 weeks for 6 weeks to induce NASH. (D) Schematic representation of the experimental mouse study. (E) Representative SEM images of the mouse livers. Scale bar: 5 μm (left) as shown on the bottom of the picture. The frequency of fenestrae was presented as porosity and quantified using image J (right). Eight-week-old Vcam1^Δend mice and Vcam1^fl/fl mice were treated with CCl4 intraperitoneally (1μL/g body weight), two time a week for 4 weeks to induce liver fibrosis. (F) Schematic representation of the experimental mouse study. Vcam1^fl/fl and Vcam1^Δend mice were injected intraperitoneally with CCl4 twice a week for 4 weeks to induce liver fibrosis. (G) Representative SEM images of the mouse livers. Scale bar: 5 μm (left) as shown on the bottom of the picture. The frequency of fenestrae was presented as porosity and quantified using image J (right). Representative images of Lyve1 immunostaining of liver sections from CD-HFD induced NASH mice (H) or CCl4 induced liver fibrosis mice (I). Scale bar: 50 μm. *, **, ***, **** indicate statistical significance with p < 0.05, p < 0.01, p < 0.001 and p < 0.0001, respectively.