Fig 2: JTE-013 alleviated fibrosis by inhibiting the expression of RHOA, YAP, and related pathway proteins in lung tissues. (A): Protein–protein-interaction network constructed using the String database; (B): Co-expression of proteins retrieved from databases; (C): Immunohistochemical staining was used to detect the expression of RHOA, YAP, CTGF, and CYR61 and their OD quantitative analysis chart (scale bar = 50 μm). (D): Immunofluorescence staining was used to detect the expression of RHOA and their quantitative analysis chart (scale bar = 200 μm). (E): Immunofluorescence staining was used to detect the colocalization of YAP and α-SMA. (F): Western blot was used to detect the expression of RHOA, TAZ, CTGF, CYR61, and the phosphorylation of Lats1 and YAP. Their relative levels were analyzed and compared. (** p < 0.01 vs. control group, ## p < 0.01 vs. BLM group, && p < 0.01 vs. BLM + JTE-013 group). Original Western blot available in Supplementary Materials.

Fig 3: Schematic representation of the role of JTE-013 in pulmonary fibrosis. JTE-013 or S1PR2 knockdown inhibited the binding of S1P and S1PR2 to regulate the RHOA/YAP pathway. This further affected the downstream CTGF/CYR61 expression and mitochondrial dynamics, promoted mitochondrial fusion and the phenotypic transition of MFN, inhibited mitochondrial fission, down-regulated the phosphorylation level of Fis1 and Drp1, and reduced the production of mitochondrial ROS and ROS, thereby alleviating pulmonary fibrosis.