Hepatic microenvironment underlies fibrosis in chronic hepatitis B patients

Figure 1 Profiling of fibrosis marker genes in liver samples from patients with hepatitis B virus infection. qPCR of fibrosis marker genes in hepatitis B virus patients with advanced fibrosis (S3-4, n = 16) compared to patients with less fibrosis (S0-1, n = 16). Values presented are expressed as the means ± SE; Statistical comparisons were made using the Mann–Whitney–Wilcoxon test; P value < 0.05 was considered significant; ^aP < 0.05; ^bP < 0.01; ^cP < 0.001. FAP: Fibroblast activation protein; α-SMA: Alpha-smooth muscle actin; TIMP1: Tissue inhibitor of metalloproteinase 1; COL1A1: Collagen type 1 alpha 1 chain; TLR4: Toll-like receptor 4.

Figure 2 Profiling of inflammatory factors and growth factors in liver samples from patients with hepatitis B virus infection. A: qPCR of inflammatory factors; and B: Growth factors in hepatitis B virus patients with advanced fibrosis (S3-4, n = 16) compared to patients with less fibrosis (S0-1, n=16). Values presented are expressed as the means ± SE; P value < 0.05 was considered significant; ^aP < 0.05; ^bP < 0.01; ^cP < 0.001; ns: Non-significant. IL-1β: Interleukin 1β; TNF-α: Tumor necrosis factor alpha; TGF-β1: Transforming growth factor β1; PDGF: Platelet-derived growth factor; CTGF: Connective tissue growth factor.

Figure 3 Activation of hepatic stellate cells with growth factors and inflammatory factors. A: qPCR of fibroblast activation genes in LX-2 cells treated with various growth factors or cytokines for 16 h; B: qPCR of fibroblast activation genes in LX-2 cells treated with platelet-derived growth factor for 48 h. Values presented are expressed as the means ± SE; P value < 0.05 was considered significant; ^aP < 0.05; ^bP < 0.01; ^cP < 0.001. α-SMA: Alpha-smooth muscle actin; COL1A1: Collagen type 1 alpha 1 chain; TIMP1: Tissue inhibitor of metalloproteinase 1; TGF-β1: Transforming growth factor β1; PDGF: Platelet-derived growth factor; CTGF: Connective tissue growth factor.

Figure 4 Hepatic stellate cells may serve as a proinflammatory source. A: qPCR inflammation signature genes in LX-2 cells treated with various growth factors or cytokines; B: qPCR of alpha-smooth muscle actin, interleukin 1β and platelet-derived growth factor gene levels in LX-2 cells treated with transforming growth factor β1 combined with interleukin 1β. Values presented are expressed as the means ± SE; P value < 0.05 was considered significant; ^aP < 0.05; ^bP < 0.01; ^cP < 0.001. IL-1β: Interleukin 1β; IL6: Interleukin 6; CCL3: C-C motif chemokine ligand 3; α-SMA: Alpha-smooth muscle actin; PDGF: Platelet-derived growth factor.