title: Vanadium pentoxide (V(2)O(5)) induced mucin production by airway epithelium.
abstract: Exposure to environmental pollutants has been linked to various airway diseases and disease exacerbations. Almost all chronic airway diseases such as chronic obstructive pulmonary disease and asthma are caused by complicated interactions between gene and environment. One of the major hallmarks of those diseases is airway mucus overproduction (MO). Excessive mucus causes airway obstruction and significantly increases morbidity and mortality. Metals are major components of environmental particulate matters (PM). Among them, vanadium has been suggested to play an important role in PM-induced mucin production. Vanadium pentoxide (V(2)O(5)) is the most common commercial source of vanadium, and it has been associated with occupational chronic bronchitis and asthma, both of which are MO diseases. However, the underlying mechanism is not entirely clear. In this study, we used both in vitro and in vivo models to demonstrate the robust inductions of mucin production by V(2)O(5). Furthermore, the follow-up mechanistic study revealed a novel v-raf-1 murine leukemia viral oncogene homolog 1-IKK-NF-κB pathway that mediated V(2)O(5)-induced mucin production. Most interestingly, the reactive oxygen species and the classical mucin-inducing epidermal growth factor receptor (EGFR)-MAPK pathway appeared not to be involved in this process. Thus the V(2)O(5)-induced mucin production may represent a novel EGFR-MAPK-independent and environmental toxicant-associated MO model. Complete elucidation of the signaling pathway in this model will not only facilitate the development of the treatment for V(2)O(5)-associated occupational diseases but also advance our understanding on the EGFR-independent mucin production in other chronic airway diseases.
authors.affiliation: Division of Translational Biology, the Hamner Institutes for Health Research, Brody School of Medicine, East Carolina University, North Carolina, USA.
authors.forename: Dongfang
authors.initials: D
authors.lastname: Yu
authors.forename: Dianne M
authors.initials: DM
authors.lastname: Walters
authors.forename: Lingxiang
authors.initials: L
authors.lastname: Zhu
authors.forename: Pak-Kei
authors.initials: PK
authors.lastname: Lee
authors.forename: Yin
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D066246:ErbB Receptors / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008679:Metaplasia; D051379:Mice; D055271:Mucin 5AC / Q000096:biosynthesis* / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D011014:Pneumonia / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D017968:Vanadium Compounds / Q000633:toxicity*; D048490:raf Kinases / Q000378:metabolism
chemical_list: D016166:Free Radical Scavengers; D055271:Mucin 5AC; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D017968:Vanadium Compounds; C066075:vanadium pentoxide; D066246:ErbB Receptors; D048490:raf Kinases; D051550:I-kappa B Kinase