In vitro cadmium effects on ECM gene expression in human bronchial epithelial cells

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 MIT assay were performed. We also investigated whether an imbalance in the TGF beta/TGF beta receptor (TGF beta R) expression mediated Cd effects. The results showed the sub-toxic Cd dose significantly increased tenascin, vitronectin, beta 1 and beta 5 integrin gene expression. The toxic Cd dose decreased type IV and V collagen, alpha 1, alpha 2 and beta 3 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 TGF beta 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 TGF beta/TGF beta R signaling. (C) 2014 Elsevier Ltd. All rights reserved.