title: In vitro cadmium effects on ECM gene expression in human bronchial epithelial cells.
abstract: Occupational and environmental exposure to the heavy metal cadmium (Cd) and its inhalation from cigarette smoke are associated with emphysema. Many growth factors and extracellular matrix (ECM) cell signaling molecules are directly involved in the epithelial bronchial cell pathway. This study investigated the direct effects of Cd on the production of several ECM components in human bronchial epithelial cells (BEAS-2B) that were exposed in vitro for 48 h to sub-toxic and toxic concentrations of Cd. Gene expression of collagens, metalloproteases (MMPs), integrins, tenascin and vitronectin were quantified by RT-PCR. To study apoptosis cascade, annexin assay and cellular cytotoxicity by MTT assay were performed. We also investigated whether an imbalance in the TGFβ/TGFβ receptor (TGFβR) expression mediated Cd effects. The results showed the sub-toxic Cd dose significantly increased tenascin, vitronectin, β1 and β5 integrin gene expression. The toxic Cd dose decreased type IV and V collagen, α1, α2 and β3 integrins. Both Cd doses down-regulated type I collagen and up-regulated metalloproteases. Each Cd dose caused a different imbalance in the complex pattern of TGFβ and its receptors. No alteration in classic apoptotic marker protein expression was observed in presence of the sub-toxic dose of Cd, suggesting this metal alters ECM production without apoptotic activation. In conclusion, all these data show even sub-toxic Cd dose exposure alters the specific gene expression of several ECM components that are crucially implicated in the mechanical properties of lung parenchyma supporting the hypothesis that the mechanism underlying Cd-induced lung disease may involve downstream changes in TGFβ/TGFβR signaling.
authors.affiliation: Department of Experimental Medicine, University of Perugia, Perugia, Italy. Electronic address: tiziano.baroni@unipg.it.
authors.forename: Tiziano
authors.initials: T
authors.lastname: Baroni
authors.affiliation: Department of Experimental Medicine, University of Perugia, Perugia, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Lilli
authors.affiliation: Department of Experimental Medicine, University of Perugia, Perugia, Italy.
authors.forename: Catia
authors.initials: C
authors.lastname: Bellucci
authors.affiliation: Department of Experimental Medicine, University of Perugia, Perugia, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Luca
authors.affiliation: Department of Experimental Medicine, University of Perugia, Perugia, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Mancuso
authors.affiliation: Department of Experimental Medicine, University of Perugia, Perugia, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Fallarino
authors.affiliation: Department of Experimental Medicine, University of Perugia, Perugia, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Falabella
authors.affiliation: Department of Experimental Medicine, University of Perugia, Perugia, Italy.
authors.forename: Iva
authors.initials: I
authors.lastname: Arato
authors.affiliation: Department of Experimental Medicine, University of Perugia, Perugia, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Calvitti
authors.affiliation: Department of Experimental Medicine, University of Perugia, Perugia, Italy.
authors.forename: Lorella
authors.initials: L
authors.lastname: Marinucci
authors.affiliation: Department of Medicine, University of Perugia, Perugia, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Muzi
authors.affiliation: Department of Medicine, University of Perugia, Perugia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Dell'Omo
authors.affiliation: Department of Medicine, University of Perugia, Perugia, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Gambelunghe
authors.affiliation: Department of Experimental Medicine, University of Perugia, Perugia, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Bodo
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001980:Bronchi / Q000166:cytology*; D002104:Cadmium / Q000633:toxicity*; D002460:Cell Line; D003094:Collagen / Q000235:genetics; D015536:Down-Regulation; D004847:Epithelial Cells / Q000187:drug effects*; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D016023:Integrins / Q000235:genetics; D045726:Metalloproteases / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D019063:Tenascin / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000378:metabolism; D015854:Up-Regulation; D019096:Vitronectin / Q000235:genetics
chemical_list: D016326:Extracellular Matrix Proteins; D016023:Integrins; D019063:Tenascin; D016212:Transforming Growth Factor beta; D019096:Vitronectin; D002104:Cadmium; D003094:Collagen; D045726:Metalloproteases
keywords: Apoptosis; Cadmium; Epithelial bronchial cells; Extracellular matrix; Transforming growth factor