Hypoxia-inducible Factor 1 Mediates Nasal Polypogenesis by Inducing Epithelial-to-Mesenchymal Transition

Abstract

hNECs undergo EMT during hypoxia and this process is critically mediated by HIF-1α and pSmad3. This study shows that hypoxia-induced EMT is likely to contribute to nasal polyposis in CRS, and suggests that HIF-1α be viewed as a therapeutic target for nasal polyposis.

Hypoxia increases extracellular fibronectin abundance but not assembly during epithelial cell transdifferentiation

“…S1A). We obtained similar results using human lung alveolar A549 cells, which undergo EMT upon exposure to TGF-b (Haynes et al, 2011) and hypoxia (Shin et al, 2012). Although EMT of A549 cells upon hypoxia took 7 days, as indicated by increased fibronectin and actin stress fibers, the fibronectin fibrils seen with TGF-b were mostly absent (supplementary material Fig.…”

New Insights into Upper Airway Innate Immunity

“…Abnormalities that affect epithelial cilia function may also result in impaired mucociliary clearance. 28 31 either of which can lead to decreased mucociliary clearance. In fact, there is evidence that these near-anaerobic conditions may significantly contribute to the pathogenesis of CRS.…”

Overexpressed proprotein convertase 1/3 induces an epithelial-mesenchymal transition in airway epithelium

“…In addition, PC1/3 cells display downregulation of epithelial markers and upregulation of mesenchymal markers, referred to as EMT [2,4]. Recently, SHIN et al [8] showed hypoxia-induced EMT via a SMAD3-dependent mechanism in cultured human nasal epithelial cells and in epithelial cells lining nasal polyps, suggesting an important role for EMT in the pathogenesis of nasal polyps. Our proteomic analysis shows that differentially produced proteins between PC1/3 cells and mock cells are implicated in carbohydrate metabolism, cell proliferation, cytoskeletal reorganisation, DNA metabolism and signal transduction (online supplementary figure S1 and table S2).…”

“…Interestingly, the expression levels of N-cadherin, snail and twist were significantly higher in cytomix-treated NHNE cells compared to TGF-b1-treated cells. Moreover, PC1/ 3 expression was induced by cytomix, but not by TGF-b1, indicating the involvement of PC1/3 in cytomixmediated EMT, but not in TGF-b1-induced EMT; TGF-b1 signalling was examined by measuring the levels of phospho-SMAD3 (p-SMAD3) [8]. We further examined the relationships between PC1/3 and EMT markers in nasal polyps and found that PC1/3 expression was positively correlated with loss of E-cadherin…”

“…There is increasing evidence that lung epithelial injury and abnormal epithelial repair responses induce the persistent epithelial activation leading to pathological processes associated with tissue fibrosis by undergoing EMT [6,7]. Recently, it has been shown that a-SMA is expressed in epithelial cell lining in nasal polyps and hypoxia-induced EMT via a SMAD (mothers against decapentaplegic homologue)-3-dependent mechanism in cultured human nasal epithelial cells [8], indicating an important role for EMT in the pathogenesis of nasal polyps.…”