PULMONARY fibrosis (PF), a severe form of lung disease, often leads to irreversible lung damage, and macrophages play a critical role in its progression. New research sheds light on the significant role of YAP and TAZ, two proteins activated in macrophages in PF patients and in animal models. This study uncovers the pivotal function of YAP/TAZ signaling in the inflammatory and fibrotic processes within PF.
Researchers focused on the effects of YAP/TAZ in macrophages after bleomycin-induced PF. Their findings revealed that deleting YAP/TAZ specifically in macrophages led to reduced inflammation and fibrosis, providing insight into how YAP/TAZ activation accelerates the condition. Interestingly, a constitutively active form of YAP (YAP5SA) made PF worse by enhancing macrophage recruitment, promoting inflammation, and impairing cell regeneration. In contrast, blocking key signaling pathways in this process prevented the exacerbation of PF.
The study also highlighted a crucial signaling axis involving YAP/TAZ, CCL2, and TGFβ1. This axis regulates macrophage polarization and their interaction with lung fibroblasts, driving the transition from fibroblasts to myofibroblasts—a key process in fibrosis. These findings suggest that targeting YAP/TAZ activity may be an effective approach for PF treatment, potentially halting or even reversing its progression.
With these discoveries, YAP/TAZ emerge as promising targets in the development of therapies aimed at managing pulmonary fibrosis, offering hope for improved patient outcomes.
Reference: Mia MM et al. YAP/TAZ are Crucial Regulator of Macrophage-mediated Pulmonary Inflammation and Fibrosis after Bleomycin-induced Injury. Eur Respir J. 2025. doi:10.1183/13993003.01544-2023.
Anaya Malik | AMJ
