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

Abstract

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.

β-elemene alleviates esophageal fibrosis after endoscopic submucosal dissection via the FAP-mediated PTEN-PI3K/AKT signaling pathway

“…Our findings revealed that β-elemene can inhibit the proliferation of PHEGFs and induce their apoptosis in a concentration-dependent manner. This finding is in line with previous research indicating that β-elemene has the ability to suppress the proliferation of tracheal granulation fibroblasts and mitigate airway stenosis [ 36 , 37 ]. The PI3K/AKT signaling pathway, a classic intracellular signal transduction pathway, governs diverse biological processes, including cell survival, apoptosis, migration, proliferation, and inflammatory responses [ 38 ].…”

β-Elemene Attenuates Fibrosis after Esophageal Endoscopic Submucosal Dissection via Modulating the HIF-1α/HK2/p38-MAPK Signaling Axis

“…It should also be noted that there may exist other regulatory mechanisms underlying the effect of β-elemene on fibroblasts. Xue et al suggested that β-elemene attenuated the proliferation of human airway granulation fibroblasts through suppressing the TGF-beta/Smad signaling pathway . Another study, although it corroborates our study in regard to the p38MAPK signaling pathway, indicated that β-elemene functioned as a trigger for apoptosis of human rheumatoid arthritis fibroblast-like synoviocytes through reactive oxygen species-dependent activation of p38MAPK .…”

“…Xue et al suggested that β-elemene attenuated the proliferation of human airway granulation fibroblasts through suppressing the TGF-beta/Smad signaling pathway. 25 Another study, although it corroborates our study in regard to the p38MAPK signaling pathway, indicated that βelemene functioned as a trigger for apoptosis of human rheumatoid arthritis fibroblast-like synoviocytes through reactive oxygen species-dependent activation of p38MAPK. 20 Herein, the complex mechanistic actions by which β-elemene modulates fibroblasts merit further investigations.…”

Plumbagin attenuates traumatic tracheal stenosis in rats and inhibits lung fibroblast proliferation and differentiation via TGF-β1/Smad and Akt/mTOR pathways

“…It has been found that TGF-β1 is overexpressed in benign airway stenosis [ 12 , 33 ]. The levels of Smad2 and Smad3 have also been shown to increase in human airway granulation fibroblasts in vitro [ 34 ]. In the present study, TGF-β1 protein levels were elevated in TS rats, and this effect was attenuated by PLB.…”