TGF-β3 Promotes MUC5AC Hyper-Expression by Modulating Autophagy Pathway in Airway Epithelium

Zhang, Yun; Tang, Hongmei; Yuan, Xiefang; Qin, Ran; Wang, Xing; Song, Qibin; Zhang, Lei; Qiu, Yuhuan

doi:10.1016/j.ebiom.2018.06.032

Cited by 21 publications

(22 citation statements)

References 56 publications

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“…Our data suggested that the inhibition of ROS production by NAC in TGF-β3-activated epithelial cells significantly decreased autophagy flux (Figures 3(a)-3(d)). We previously found that TGF-β3 stimulation in the epithelial cells was associated with an increase in mucus production and autophagy was required for TGF-β3-induced MUC5AC levels in 16HBE cells [24]. In this study, immunofluorescence staining revealed that MUC5AC protein was significantly reduced in 16HBE cells treated with TGF-β3 and NAC compared to 16HBE cells treated with TGF-β3 only (Figures 3(e) and 3(f)).…”

Section: Tgf-β3supporting

confidence: 58%

“…Smad2-siRNA lentivirus vectors and Smad3-siRNA lentivirus vectors were purchased from GeneChem Technology (Shanghai, China). 16HBE cells (2 × 10 5 /ml) were transduced as previously described [24].…”

Section: Cell Culture Transfection and Lentiviral Transductionmentioning

confidence: 99%

“…TGF-β1 promotes autophagy through the generation of ROS in renal tubular epithelial cells [23]. Moreover, previous observations have suggested that autophagy is considered as an important aspect of biological effects of TGF-β3 in modulating airway mucus hypersecretion [24]. However, the exact mechanism of the relationship between TGF-β3-induced autophagy and ROS remains unclear.…”

Section: Introductionmentioning

confidence: 99%

“…Evidence has shown that ROS can influence TGF-β signaling via various pathways, including the Smad pathway, MAPK (such as p38) pathway, and Rho-GTPase pathway [50]. Our previous study has demonstrated that TGF-β3 induces autophagy activity and that downstream mucus secretion is Smad2/3 signaling pathway-dependent [24]. Collectively, these studies urged us to further investigate TGF-β3induced mucus secretion in asthma via ROS-dependent mechanism.…”

mentioning

confidence: 97%

“…NOX enzymes are a family of NADPH-dependent oxygen reductases that are widely expressed in eukaryotes [54]. TGF-β is widely expressed in inflammatory cells infiltrated in the bronchial mucosal but also in structural cells of the airway wall including epithelial and endothelial cells [24]. TGF-β induces the epithelial-to-mesenchymal transition (EMT) associated with NOX4, which is a TGF-β/Smad3-inducible source of reactive oxygen species (ROS) affecting cell migration and fibronectin expression [55].…”

mentioning

confidence: 99%

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TGF-β3 Induces Autophagic Activity by Increasing ROS Generation in a NOX4-Dependent Pathway

Zhang

Tang

Liu

et al. 2019

Mediators of Inflammation

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Higher concentrations of reactive oxygen species (ROS) have been associated with epithelial cell damage, cell shedding, and airway hyperresponsiveness. Previous studies have indicated that transforming growth factor-beta (TGF-β) mediates ROS production and NADPH oxidase (NOX) activity. In our previous study, we also observed that TGF-β3 increases mucus secretion in airway epithelial cells in an autophagy-dependent fashion. Although it is well known that the relationship between ROS and autophagy is cell context-dependent, the exact mechanism of action remains unclear. The following study examined whether ROS act as upstream of autophagy activation in response to TGF-β3 induction. Using an allergic inflammation mouse model induced by house dust mite (HDM), we observed elevated lung amounts of TGF-β3 accompanied by increased ROS levels. And we found that ROS levels were elevated and NOX4 expression was increased in TGF-β3-induced epithelial cells, while the lack of NOX4 in the epithelial cells could reduce ROS generation and autophagy-dependent MUC5AC expression treated with TGF-β3. Furthermore, our studies demonstrated that the Smad2/3 pathway was involved in TGF-β3-induced ROS generation by promoting NOX4 expression. The inhibition of ROS generation by N-Acetyl-L-cysteine (NAC) resulted in a decrease in mucus expression and autophagy activity in vivo as well as in vitro. Finally, TGF-β3-neutralizing antibody significantly reduced the ROS generation, mucus expression, and autophagy activity and also decreased the phosphorylation of Smad2 and Smad3. Taken together, the obtained results revealed that persistent TGF-β3 activation increased ROS levels in a NOX4-dependent pathway and subsequently induced autophagy as well as MUC5AC expression in the epithelial cells.

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Section: Tgf-β3supporting

confidence: 58%

Section: Cell Culture Transfection and Lentiviral Transductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 97%

mentioning

confidence: 99%

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TGF-β3 Induces Autophagic Activity by Increasing ROS Generation in a NOX4-Dependent Pathway

Zhang

Tang

Liu

et al. 2019

Mediators of Inflammation

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Fibroblast-to-myofibroblast transition in bronchial asthma

Michalik

Wójcik-Pszczoła

Paw

et al. 2018

Cell. Mol. Life Sci.

118

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Bronchial asthma is a chronic inflammatory disease in which bronchial wall remodelling plays a significant role. This phenomenon is related to enhanced proliferation of airway smooth muscle cells, elevated extracellular matrix protein secretion and an increased number of myofibroblasts. Phenotypic fibroblast-to-myofibroblast transition represents one of the primary mechanisms by which myofibroblasts arise in fibrotic lung tissue. Fibroblast-to-myofibroblast transition requires a combination of several types of factors, the most important of which are divided into humoural and mechanical factors, as well as certain extracellular matrix proteins. Despite intensive research on the nature of this process, its underlying mechanisms during bronchial airway wall remodelling in asthma are not yet fully clarified. This review focuses on what is known about the nature of fibroblast-to-myofibroblast transition in asthma. We aim to consider possible mechanisms and conditions that may play an important role in fibroblast-to-myofibroblast transition but have not yet been discussed in this context. Recent studies have shown that some inherent and previously undescribed features of fibroblasts can also play a significant role in fibroblast-to-myofibroblast transition. Differences observed between asthmatic and non-asthmatic bronchial fibroblasts (e.g., response to transforming growth factor β, cell shape, elasticity, and protein expression profile) may have a crucial influence on this phenomenon. An accurate understanding and recognition of all factors affecting fibroblast-to-myofibroblast transition might provide an opportunity to discover efficient methods of counteracting this phenomenon.

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Autophagy in chronic lung disease

Racanelli

Choi

2020

Progress in Molecular Biology and Translational Science

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TGF-β3 Promotes MUC5AC Hyper-Expression by Modulating Autophagy Pathway in Airway Epithelium

Cited by 21 publications

References 56 publications

TGF-β3 Induces Autophagic Activity by Increasing ROS Generation in a NOX4-Dependent Pathway

TGF-β3 Induces Autophagic Activity by Increasing ROS Generation in a NOX4-Dependent Pathway

Fibroblast-to-myofibroblast transition in bronchial asthma

Autophagy in chronic lung disease

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