title: Akt induces down regulation of MUC5AC production in NCI-H292 human airway epithelial cells cultured on extracellular matrix.
abstract: MUC5AC mucin overproduction is a key feature of asthma as contributes to airway obstruction. The production of MUC5AC is regulated in part by signals from extracellular matrix via integrin pathways, but it remains largely unclear. We investigated the role of Akt, a typical signal transducer in the integrin pathway, in the regulation of MUC5AC production. When NCI-H292 human airway epithelial cells were cultured on laminin or Matrigel, we found that the activity of Akt was suppressed, as compared to control cells with upregulated MUC5AC production. In contrast, Akt was activated in cells cultured on type IV collagen with downregulated MUC5AC production. The Akt inhibitor induced upregulation of MUC5AC. In contrast, overexpression of active Akt induced downregulation of MUC5AC production. These results suggest that a signal from laminin or Matrigel induces upregulation of MUC5AC by suppressing Akt activity, whereas a signal from type IV collagen induces downregulation of MUC5AC, mediated by Akt activation.
authors.affiliation: a Faculty of Bioresource Sciences, Akita Prefectural University , Akita , Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Iwashita
authors.forename: Yuho
authors.initials: Y
authors.lastname: Ito
authors.forename: Mari
authors.initials: M
authors.lastname: Yokoo
authors.forename: Sunao
authors.initials: S
authors.lastname: Takahashi
authors.forename: Jun
authors.initials: J
authors.lastname: Murata
mesh_terms: D045744:Cell Line, Tumor; D003094:Collagen / Q000494:pharmacology; D024141:Collagen Type IV / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D004338:Drug Combinations; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007797:Laminin / Q000494:pharmacology; D055271:Mucin 5AC / Q000096:biosynthesis*; D009093:Mucus / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011509:Proteoglycans / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012137:Respiratory System / Q000166:cytology*
chemical_list: D024141:Collagen Type IV; D004338:Drug Combinations; D007797:Laminin; D055271:Mucin 5AC; D016328:NF-kappa B; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt; MUC5AC; asthma; extracellular matrix; type IV collagen