Fig. 3

Overview of molecular signaling pathways in PF. In the TGF-β signaling, TGF-β binding to TGF-βRs activates the TGF-β-Smad signalings. In the Wnt signaling, activated DVL inhibits the destruction complex and then allows β-catenin accumulation to enter the nucleus where it can act together with either p300 or CBP as a transcriptional co-activator for TCF/LEF to activate Wnt-related fibrotic genes. In the Wnt signaling, MAP4K and TAOK families of kinases phosphorylate and activate LATS1/2. Meanwhile, YAP activity is regulated by the LATS1/2 kinases, which promote YAP nucleus accumulation and bind to several transcription factors, such as the TEAD family, eventually changing profibrotic gene expression. In the PI3K-Akt signaling, PI3Ks can be activated by various growth factors like VEGF, PDGF, and TGF-β. The common downstream of receptor-mediated PI3K activation is Akt, which regulates the activity of mTOR, HIF-1α, and Fox3 to involve cell proliferation, differentiation, and ECM deposition in PF. Image Created in https://BioRender.com