Pulmonary fibrosis and the TGF-β signaling axis: Advances in targeted therapeutics.

Pulmonary fibrosis (PF) is a chronic progressive lung disease characterised by interstitial inflammation and abnormal repair, which is a multi-step pathological process with few available therapies. The transforming growth factor-β (TGF-β) signaling cascade exerts central regulation in fibrosis and has been identified as an important pharmacological target for fibrotic diseases. In this review, we comprehensively elaborate on the current knowledge of the TGF-β/Smad axis and its directly downstream or upstream interconnected pathways, including the PI3K/Akt, MAPK, Wnt and Rho-family GTPase pathways, and their molecular effects in PF. We also summarize the major networks targeted by small-molecule inhibitors, biologics, natural products and multi-target combination regimens in the past few years. Finally, we analyzed the limitations of this study and possible directions for future research.