Fig 2: BA-specific deletion of c-Kit inhibits the denervation-induced lipid accumulation and reduces SCD1 in the BAs of BAT.a Diagram of the experimental procedure for the unilateral denervation of BAT in 8-week-old control (Con) and c-Kit?BA mice, and harvest BAT (I-BAT and D-BAT) 3 or 5 days later for the analyses. b, c Representative immunoblotting and comparisons of c-Kit, ACL, ACC, FASN, and SCD1 in the I-BAT and D-BAT 3 days after the unilateral denervation (I-BAT3 or D-BAT3). The same amount of protein loading in each lane is verified by immunoblotting of tubulin. Each dot indicates a value from one mouse and n = 6 mice/group from two independent experiments. Horizontal and vertical bars indicate mean ± SD. *,#P < 0.05 versus Con I-BAT3 or c-Kit?BA I-BAT3 by one-way ANOVA test followed by Tukey’s post-hoc test. Protein sizes are indicated as kilodalton (kDa). d, e Representative images and comparisons of the populations of different sizes of lipid droplets in the CD147+ BAs of BAT among the indicated groups. White arrowheads indicate the lipid droplets whose size is larger than 51 µm2 in CD147+ BA. Scale bars, 20 µm. Each dot indicates the population (%) of the total of 1200–2400 droplets (100%) from three portions of BAT in one mouse and n = 5 mice/group from two independent experiments. Vertical bars indicate mean ± SD. *P < 0.05 by two-way ANOVA test followed by Sidak test. NS not significant.

Fig 3: Meplazumab prevents pulmonary fibrosis caused by SARS-CoV-2. a hCD147 mice were inoculated via the intranasal with 3 × 105 TCID50 of SARS-CoV-2 and treated with CD147 antibody meplazumab at 1 d.p.i. and 7 d.p.i. Samples were collected at 2, 6, 13, 20 and 27 d.p.i. b H&E staining and Masson’s trichrome staining of lung tissue sections from the IgG and meplazumab groups at different time points. Black scale bars, 2 mm. Yellow scale bars, 100 µm. c Statistics of the positive area of Masson’s trichrome staining. n = 3 mice for each group, two-tailed unpaired t-test. d TEM analysis of lung tissues from the IgG and meplazumab groups. Black scale bars, 20 µm; yellow scale bars, 2 µm. The stars indicate collagen fibrils. e Immunofluorescence staining and quantification of a-SMA in lung tissue sections from the IgG and meplazumab groups. Scale bars, 100 µm. n = 12 images from three mice for each group, one-way ANOVA followed by multiple comparisons. f Gene expression of TGF-ß, PDGF, MMP2, MMP9, TIMP1, TIMP2, COL1A1 and COL1A2 in lung homogenates determined by RT-qPCR, compared with the corresponding IgG controls at indicated time points. GAPDH is used as a reference gene. g Gene expression of a-SMA, COL1A1, COL1A2, MMP2 and MMP9 in MRC-5 cells pre-incubated with IgG or meplazumab (60 µg/mL) followed by stimulation of TGF-ß (10 ng/mL), determined by RT-qPCR. GAPDH is used as a reference gene

Fig 4: Ablation of CD147 in fibroblasts reverses pulmonary fibrosis in the bleomycin model. a Representative multiplex immunohistochemistry staining of lung tissue sections from bleomycin-induced pulmonary fibrosis model (13 d) for α-SMA and FSP1. Scale bars, 200 μm. b Representative multiplex immunohistochemistry staining of lung tissue sections from bleomycin-induced CD147f/fFSP1-Cre and CD147f/f mice treated with or without tamoxifen (TAM) for α-SMA and CD147. Scale bars, 50 μm. c Statistics of the percentages of cells expressing CD147 in cells positive for α-SMA. n = 9 images from three mice for each group, one-way ANOVA followed by multiple comparisons. d Percentages of α-SMA fibroblasts+ and CD147-expressing α-SMA+ fibroblasts detected by flow cytometry in lung tissues of bleomycin-induced pulmonary fibrosis model. e H&E staining and Masson’s trichrome staining of lung tissues from CD147f/fFSP1-Cre and CD147f/f mice treated with or without tamoxifen at indicated time points after bleomycin administration. Scale bars, 1 cm. f Statistics of the positive area of Masson’s trichrome staining. n = 3 mice for each group, one-way ANOVA followed by multiple comparisons. g Gene expression of COL1A1, COL1A2 and COL3A1 in lung homogenates determined by RT-qPCR. GAPDH is used as a reference gene. h Hydroxyproline content from CD147f/fFSP1-Cre and CD147f/f mice treated with or without tamoxifen at 13 days after bleomycin administration. CD147f/f mice receiving PBS serves as control group. n = 3 mice for each group, one-way ANOVA followed by multiple comparisons. i TEM analysis of lung tissues from bleomycin-induced CD147f/fFSP1-Cre and CD147f/f mice at indicated time points. Black scale bars, 20 μm; yellow scale bars, 2 μm. The stars indicate collagen fibrils. j Immunofluorescence staining and quantification of α-SMA in lung tissue sections from bleomycin-induced CD147f/fFSP1-Cre and CD147f/f mice at indicated time points. Scale bars, 100 μm. n = 12 images from three mice for each group, one-way ANOVA followed by multiple comparisons. k KEGG enrichment analysis of pathways enriched in downregulated genes in lungs of CD147f/fFSP1-Cre mice compared with CD147f/f mice. l Heatmap of genes associated with cytokines-cytokine receptor interaction and ECM remodeling at indicated time points. In panel a, b and j, the rabbit or mouse IgG isotype control was used along with the staining of each molecule

Fig 5: CD147 knockdown inhibits activation of lung fibroblasts upon TGF-ß stimulation. a MRC-5 cells were transfected with shRNA for CD147 gene silence and stimulated with TGF-ß (10 ng/mL) for 24 h. The gene expression levels of CD147, a-SMA and COL1A1 were detected by real-time PCR. n = 3 samples for each group, one-way ANOVA followed by multiple comparisons. b The statistically significant profile by trend analysis of differentially expressed genes in MRC-5 cells transfected with CD147 shRNA with or without stimulation of TGF-ß. c KEGG enrichment analysis of pathways enriched in the profile in b. d Heatmap of significantly enriched genes in the profile. Columns represent samples and rows represent genes. Gene expression levels in the heat maps are z score–normalized values determined by log2[CPM] values