Fig 2: uPA-uPAR regulates the PPAR signalling pathway. (A) KEGG pathway enrichment analysis. (B) Cluster analysis of the different protein expression between fibroblasts of uPAR knockdown and control groups. (C) mRNA levels of PPARa, PPARß, and PPAR? in uPAR-siRNA treated fibroblasts and control groups. (D) PPAR? agonist reversed the effects of silencing uPAR on the expression of fibrotic factors in fibroblasts. qRT-PCR assay was used to analyze the mRNA levels of COL1, a-SMA, TGFß, FGFR1 and Ets-1. (E) Analysis of signaling pathway related proteins by western blot. (F) PPAR? agonist reversed the effects of silencing uPAR on cell migration. *P < 0.05, **P < 0.01 and ***P < 0.001 when compared between the denoted groups.

Fig 3: Inhibition of PAI-1 and the addition of uPA attenuate skin fibrosis in vivo. (A) Schematic overview of experimental design for (B, C). (B) uPAR agonist and PAI-1 inhibitor attenuate skin fibrosis, while uPAR inhibitor aggravate skin fibrosis. n = 5. Scale bar, 200 µm, 100 µm. (C) Masson staining of tissues at 21 days after drug administration. n = 5. Scale bar, 200 µm, 100 µm. (D) Quantification of dermal thickness (µm). **P < 0.01 and ****P < 0.0001 when compared between the denoted groups.

Fig 4: Inhibition of PAI-1 and the addition of uPA inhibit the expression of fibrosis associated proteins in vivo. (A, B) The proteins of a-SMA and type I collagen were detected from skins of mouse models by western blot assay. (C, D) Quantification of (A, B). (E) Skin tissues were immunohistochemically stained for type I collagen. Scale bar, 100 mm. (F) Skin tissues were immunohistochemically stained for a-SMA. Scale bar, 100 mm. **P < 0.01 and ***P < 0.001 when compared between the denoted groups.