Cigarette smoke extract inhibits cell migration and contraction via the reactive oxygen species/adenosine monophosphate–activated protein kinase pathway in nasal fibroblasts

Abstract

Background Fibroblast migration plays a significant role in wound healing after endoscopic sinonasal surgery. Cigarette smoke extract (CSE) is a potent inhibitor of fibroblast functions including cell proliferation and migration. The purpose of the study was to determine the influence of CSE on migration and collagen gel contraction in nasal fibroblasts and investigate its underlying mechanisms. Methods Fibroblast migration was evaluated using wound healing assay and transwell migration assay. Contractile activity was assessed by collagen gel contraction assay. Reactive oxygen species (ROS) were quantified by 2′,7′‐dichlorofluorescein diacetate. Fibroblasts were treated with CSE and N‐acetylcysteine (NAC), metformin, compound C, or transfected with small interfering RNA (siRNA) to suppress adenosine monophosphate–activated protein kinase (AMPK) expression. AMPK activation was determined by Western blot. Results CSE and metformin were found to significantly reduce the migration and collagen gel contraction activity of nasal fibroblasts. Conversely, pretreatment with NAC and compound C significantly enhanced the migration and collagen gel contraction activity of fibroblasts. ROS production and AMPK phosphorylation were found to be significantly induced by CSE treatment, whereas the activity was inhibited on treatment with NAC, metformin, compound C, or AMPK siRNA. Silencing of AMPK expression was found to significantly reverse the suppressive effect of CSE in nasal fibroblasts. Conclusion CSE has an inhibitory effect on cell migration and collagen gel contraction activity via the ROS/AMPK signaling pathway in nasal fibroblasts.

Systemic factors that shape cutaneous pathological scarring

“…Smoking has long been believed to be harmful to wound healing since habitual smokers have higher rates of postsurgical complications such as infections, wound dehiscence, and tissue necrosis. 97,98 Moreover, there are multiple studies showing that smoking affects all phases of wound healing: it increases thrombus formation, 99,100 impairs the phagocytic and bactericidal activity of inflammatory cells, 101,102 inhibits fibroblast migration, 103 and reduces collagen deposition. 104 The mechanisms underlying these observations may involve but are not confined to the fact that smoking produces excessive levels of reactive oxygen species 103 and induces vitamin C deficiency.…”

Smoking and Sinonasal Disease: A Narrative Review

“…In the presence of water, airborne smoke rapidly degrades, releasing high quantities of ROS (25). Moreover, cigarette smoke exposure inhibits cell migration and collagen contraction activity in nasal fibroblasts through the ROS/ AMPK signaling pathway (26).…”

The role of cancer stromal fibroblasts in mediating the effects of tobacco-induced cancer cell growth

“…The production of a large amount of ROS is one of the most important reasons that tobacco products affect the phenotype of fibroblasts. Previous reports showed that oxidative stress caused by tobacco product in human lung, gingival or nasal fibroblasts are thought to contribute a lot in attenuates collagen gel contraction and wound healing [ 15 , 22 , 23 ]. Shin et al showed that ROS/AMPK is the downstream signal pathway respond to oxidative stress caused by tobacco products [ 22 ].…”

“…Previous reports showed that oxidative stress caused by tobacco product in human lung, gingival or nasal fibroblasts are thought to contribute a lot in attenuates collagen gel contraction and wound healing [ 15 , 22 , 23 ]. Shin et al showed that ROS/AMPK is the downstream signal pathway respond to oxidative stress caused by tobacco products [ 22 ]. The use of antioxidants can remarkably promote proliferation and migration on human fibroblasts [ 24 ].…”