β-Elemene suppresses the proliferation of human airway granulation fibroblasts via attenuation of TGF-β/Smad signaling pathway.

Background: Benign airway stenosis is easily to recur as a result of hyperplastic airway granulation tissues. Our previous study proved that a Chinese drug, β-elemene, could inhibit the proliferation of fibroblasts cultured from these tissues, which could decrease the recurrence rate of this disease.

Methods: To find out the mechanism for this effect, we first cultured normal human airway fibroblasts and human airway granulation fibroblasts with different concentrations of β-elemene for the same time or the same dose of β-elemene for different times to explore the dose/time-effect relationship between the drug and these cells. Then we used gene microarray to screen out the most important pathway by which the drug influenced human airway granulation fibroblasts. At last, we assessed the condition of this pathway in human airway granulation fibroblasts and verified the effect of this drug on this pathway.

Results: β-Elemene inhibited the proliferation of human airway granulation fibroblasts in a dose but no time-dependent manner and did not affect normal human airway fibroblasts. Affecting the expression of transforming growth factor β (TGF-β)/Smad pathway may be the key mechanism for this effect. This pathway was activated in human airway granulation fibroblasts and β-elemene inhibited it in a dose-dependent manner. This effect was similar to the pathway inhibitor, SB431542, and exogenous TGF-β could attenuate this effect.

Conclusion: These results indicated that suppressing TGF-β/Smad pathway was possibly the key mechanism by which β-elemene inhibits the proliferation of human airway granulation fibroblasts. This pathway may be a promising target to treat benign airway stenosis.