Fig. 4: Monoclonal antibody targeted human PEAR1 for PF therapy.

a The mRNA expression levels of extracellular matrix genes in human pulmonary fibroblasts (HFL1) treated with 1 µg/mL anti-human PEAR1 monoclonal antibodies (LF2) by qPCR (n = 3 biologically independent samples in each group). LF2 is a humanized antibody with an ADCC/ADCP-weak human IgG4 Fc with S228P mutation. b Survival curves of humanized Pear1 mice induced by 1.5 µg/g (body weight) bleo treated with 300 mg/kg pirfenidone daily by gavage (PFD), 0.5 mg/kg (LF2L), 1 mg/kg (LF2H) LF2 through the trachea once a week. Saline was used as control (Ctrl) (n = 11 mice in Ctrl group; n = 16 mice in PFD group; n = 12 mice in LF2L group and n = 10 mice in LF2H group). c FVC was measured of Ctrl group mice, PFD group mice, LF2L group mice, and LF2H group mice (n = 3 mice in Ctrl group; n = 11 mice in PFD group; n = 7 mice in LF2L group; n = 9 mice in LF2H group). d Representative images of masson staining on lung sections from Ctrl group mice, PFD group mice, LF2L group mice, and LF2H group mice. The collagen area (green) was calculated and statistics were performed (n = 11 mice in Ctrl group; n = 16 mice in PFD group; n = 12 mice in LF2L group; n = 9 mice in LF2H group) (scale bars, 50 μm). e, f Representative images of immunofluorescence staining on lung sections from Ctrl group mice, PFD group mice, LF2L group mice, and LF2H group mice for Pdgfra (red), collagen IV (green), and DAPI (blue). The fluorescence positive area was calculated and statistics were performed (n = 11 mice in saline control group; n = 15 mice in PFD group; n = 8 mice in LF2L group; n = 8 mice in LF2H group) (scale bars, 75 μm). g A schematic diagram of the mechanism of PEAR1 in regulation of pulmonary fibrosis. ECM, extracellular matrix; MAb, monoclonal antibody. For c, d, f, one-way ANOVA was used. Data are presented as mean ± SD. Source data are provided as a Source data file.