TGF-β Signaling in the Pathogenesis of Pulmonary Fibrosis: A Review

Pulmonary fibrosis induced by PM2.5 exposure is a significant public health concern. While the central role of TGF-β1 in fibrotic signaling is well established, the crosstalk among the various signaling pathways activated by PM2.5 is not yet fully understood. A literature search was conducted in the ScienceDirect and PubMed databases using keywords such as “pulmonary fibrosis,” “PM2.5,” and “TGF-β.” Recent and high-impact articles published in English were selected, and their findings were synthesized into a narrative review. The synthesized literature reveals that PM2.5 exposure drives pulmonary fibrosis through a complex signaling network. The canonical TGF-β/Smad pathway acts as a central driver, but its pro-fibrotic effects are significantly amplified and sustained by crosstalk with non-canonical pathways (e.g., MAPK, PI3K/Akt) and other key regulatory networks like Wnt/β-catenin and Hippo/YAP. Overall, PM2.5-induced pulmonary fibrosis results from an interconnected network of pro-fibrotic signals, underscoring the need for multitargeted therapeutic approaches in the future.