Fig 2: Endothelial cells in keloids exhibit mesenchymal characteristics.a UMAP plot of endothelial cells annotated into clusters 1–12. Colors represent sample origins. b Proportion plot of fibroblast subgroups composition between keloid and hypertrophic scar. Colors represent the sample origins. c Heatmap of marker gene expression in each annotated endothelial cells. d The enrichment of KEGG for the upregulated genes in cluster 11 comparing to hypertrophic scar. e Pseudotime analysis of the sequential relationship of endothelial cell clusters in development. Dark blue is the beginning of differentiation and yellow is the end point. f UMAP plot of endothelial cells from GSE163973, GSE181318, and GSE220300 annotated as cluster 0–3 according to the previous annotation of endothelial cells clusters. Each color represents one cluster. g The bar graphs show the differences in the percentage of different endothelial cells clusters in keloids (n = 10 biologically independent samples) and scars (n = 9 biologically independent samples). Values present the means ± SEM. h Immunofluorescence staining of CD31 (green) and FN1 (red) in the dermis of human hypertrophic scars and keloids. Scale bar: 100 μm.

Fig 3: FN1 expression in EAE-induced fibrotic bladder tissue. a The expression of FN1 in bladder fibrosis with different scores was analyzed by immunohistochemistry. b The expression of FN1 in bladder fibrosis with different scores was analyzed by Western blotting. c The expression of FN1 in bladder fibrosis with different scores was analyzed by RT-qPCR. The findings were from three separate experiments. The data are expressed as the mean ± SD. NC, normal control group; CS, clinical symptoms; FN1, fibronectin 1. nsP > 0.05, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 versus control. Scale bar = 200 μm

Fig 4: AIL attenuates Bleomycine-induced pulmonary fibrosis in mice. (A) Schematic diagram outlining the treatment strategy involving AIL or JQ-1 post bleomycin (BLM)-induced pulmonary fibrosis. (B) Enhanced pause (Penh) was assessed by WBP in each group on Day 21 after modeling; n = 6. (C) Representative images of HE staining of the lung section at Day 21 after BLM-induction, Scale bars: 300 μm. (D) Ashcroft score analysis of (C), n = 6 mice per group, 2 slices per mice. (E) Representative images of Masson's trichrome staining of the lung section on Day 21 after BLM-induction, Scale bars: 300 μm. (F) Collagen volume fraction analysis of (E); n = 6 mice per group, 2 slices per mice. (G) The mRNA levels of EndMT markers Cd31, Cdh5 and Vim in lung tissues on Day 21 after BLM-induction were analyzed by qRT-PCR; n = 3. (H) The mRNA levels of Meox1 and fibrotic markers Acta2, Col1a1 and Fn1 in lung tissues on Day 21 after BLM-induction were analyzed by qRT-PCR; n = 9. (I) The expression of Meox1, Collagen I, Fibronectin and Cd31 in lung tissues of mice was analyzed by Western blotting. (J) Quantitative analysis of protein expression in (I) was performed by ImageJ software; n = 6. (K) Quantitative hydroxyproline assay of the right lung in the groups as indicated; n = 6. Data are presented as mean ± SD; #P < 0.05, ##P < 0.01, ###P < 0.001, ####P < 0.0001 by two-tailed Student's t-test; ∗P < 0.05, ∗∗P < 0.01, ∗∗∗∗P < 0.0001 by one-way ANOVA followed by Tukey's post hoc test between indicated groups.

Fig 5: miR-219c-5p targets FN1 and affects BSMC proliferation. a miR-219c-5p and FN1 3′-UTR binding and luciferase activity detection in BSMCs (n = 3). b The OD450 values of the cells were measured via CCK8 assay. The findings were from three separate experiments. The data are expressed as the mean ± SD. WT, wild type; MUT, mutant; FN1, fibronectin 1; 3′-UTR, three prime untranslated region. nsP > 0.05, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 versus mimic NC or inhibitor NC