Lentinan Alleviated PM2.5 Exposure-Induced Epithelial–Mesenchymal Transition in Pulmonary Epithelial Cells by Inhibiting the GARP/TGF-β/Smad Pathway

Summary

Air pollution particles (PM2.5) can cause serious lung damage by triggering a process called epithelial-mesenchymal transition, where lung cells lose their protective qualities. This study found that a natural compound called lentinan, derived from shiitake mushrooms, can help prevent this harmful process by blocking a protein called GARP. The research suggests that lentinan could be a promising natural treatment for lung diseases caused by air pollution.

Background

PM2.5 fine particulate matter is a significant air pollutant that can penetrate deep into lungs and cause various diseases including pulmonary fibrosis and COPD. The GARP protein acts as a key regulator of TGF-β, a cytokine implicated in PM2.5-induced pulmonary pathological changes. Lentinan is a shiitake mushroom-derived polysaccharide with known anti-inflammatory properties.

Objective

To investigate the role of GARP in PM2.5-induced epithelial-mesenchymal transition (EMT) in pulmonary epithelial cells and evaluate the therapeutic potential of lentinan in reversing this process through the TGF-β/SMAD pathway.

Results

PM2.5 treatment upregulated GARP, TGF-β1, and p-Smad2/3 proteins, promoting EMT and increasing cell migration and invasion. GARP knockdown reversed these effects. Lentinan treatment effectively inhibited the PM2.5-induced GARP/TGF-β/Smad pathway activation and alleviated EMT markers, restoring E-Cadherin expression and reducing N-Cadherin and Vimentin.

Conclusion

This study identifies GARP as a novel regulator of PM2.5-induced EMT and demonstrates that lentinan effectively alleviates this process by inhibiting GARP and the TGF-β/Smad pathway. These findings suggest potential therapeutic applications of lentinan for PM2.5-induced respiratory diseases and warrant further in vivo validation.
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