Hydrogen sulfide attenuates cigarette smoke-induced airway remodeling by upregulating SIRT1 signaling pathway.
Airway remodeling is one of the characteristics for chronic obstructive pulmonary disease (COPD). The mechanism underlying airway remodeling is associated with epithelial-mesenchymal transition (EMT) in the small airways of smokers and patients with COPD. Sirtuin 1 (SIRT1) is able to reduce oxidative stress, and to modulate EMT. Here, we investigated the effects and mechanisms of hydrogen sulfide (H2S) on pulmonary EMT in vitro and in vivo. We found that H2S donor NaHS inhibited cigarette smoke (CS)-induced airway remodeling, EMT and collagen deposition in mouse lungs. In human bronchial epithelial 16HBE cells, NaHS treatment also reduced CS extract (CSE)-induced EMT, collagen deposition and oxidative stress. Mechanistically, NaHS upregulated SIRT1 expression, but inhibited activation of TGF-β1/Smad3 signaling in vivo and in vitro. SIRT1 inhibition by a specific inhibitor EX527 significantly attenuated or abolished the ability of NaHS to reverse the CSE-induced oxidative stress. SIRT1 inhibition also abolished the protection of NaHS against CSE-induced EMT. Moreover, SIRT1 activation attenuated CSE-induced EMT by modifying TGF-β1-mediated Smad3 transactivation. In conclusion, H2S prevented CS-induced airway remodeling in mice by reversing oxidative stress and EMT, which was partially ameliorated by SIRT1 activation. These findings suggest that H2S may have therapeutic potential for the prevention and treatment of COPD.
['Guan|Ruijuan|R|', 'Wang|Jian|J|', 'Cai|Zhou|Z|', 'Li|Ziying|Z|', 'Wang|Lan|L|', 'Li|Yuanyuan|Y|', 'Xu|Jingyi|J|', 'Li|Defu|D|', 'Yao|Hongwei|H|', 'Liu|Wei|W|', 'Deng|Bingxian|B|', 'Lu|Wenju|W|']
D056151:Airway Remodeling D000818:Animals D002460:Cell Line D003094:Collagen D004195:Disease Models, Animal D058750:Epithelial-Mesenchymal Transition D005786:Gene Expression Regulation D006801:Humans D006862:Hydrogen Sulfide D008297:Male D051379:Mice D018384:Oxidative Stress D015398:Signal Transduction D056564:Sirtuin 1 D012906:Smoke D014026:Tobacco
Hydrogen sulfide Airway remodeling COPD Epithelial-mesenchymal transition Sirtuin 1 Oxidative stress