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PPARγ as an Integrator of Developmental Lung Reprogramming by Early-Life Per- and Polyfluoroalkyl Substances (PFAS)
Virender K Rehan1, Irfan Rahman2
1Department of Pediatrics, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, David Geffen School of Medicine at UCLA, Torrance, CA.
Summary
Per- and polyfluoroalkyl substances (PFAS) disrupt fetal lung development by suppressing PPARγ signaling. This molecular pathway links early-life exposure to later respiratory issues and allergic susceptibility.
Area of Science:
- Environmental Health
- Developmental Biology
- Toxicology
Background:
- Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants found in various exposure sources.
- Early-life exposure to PFAS is linked to immune dysfunction, impaired lung maturation, and increased respiratory vulnerability.
- The precise molecular mechanisms underlying PFAS effects on developing lungs are not fully understood.
Purpose of the Study:
- To propose peroxisome proliferator-activated receptor gamma (PPARγ) as a key mediator of PFAS-induced developmental lung reprogramming.
- To explore how PFAS exposure disrupts PPARγ signaling pathways during critical lung development periods.
- To provide a mechanistic framework for understanding environmentally programmed respiratory diseases.
Main Methods:
- Mini-review synthesizing existing epidemiologic and experimental evidence.
- Analysis of studies examining PFAS effects on PPARγ expression and signaling in the developing lung.
- Discussion of pharmacologic modulation of PPARγ in response to PFAS exposure.
Main Results:
- PFAS exposure in the developing lung is associated with suppressed pulmonary PPARγ expression and signaling.
- Pharmacologic modulation of PPARγ influences PFAS-induced epithelial inflammatory responses.
- PFAS-mediated disruption of PPARγ signaling may alter lipofibroblast identity, alveolar maturation, and macrophage polarization.
Conclusions:
- PPARγ acts as a central integrator of developmental lung reprogramming by PFAS.
- Disruption of PPARγ signaling by PFAS can link structural and immune reprogramming, potentially leading to allergic susceptibility.
- Understanding PFAS-perturbed PPARγ-dependent programs is crucial for addressing environmentally programmed respiratory disease.
