Expression of matrix proteins in an in vitro model of airway remodeling in asthma.
Acute asthma is characterized by a decrease in the pH of the exhaled breath condensate and bronchoconstriction. These perturbations may injure the epithelium in a chronic, intermittent pattern, leading to subepithelial fibrosis. We used an in vitro three-dimensional model of the bronchial mucosa to elucidate the response to a repeated chemical or physical insult to the epithelium in the postcontraction phase. We used enzyme-linked immunosorbent assay and reverse transcriptase--polymerase chain reaction to assess the production of the following proteins: matrix metalloproteinase (MMP) 3, MMP-9, tissue inhibitor of MMP-1, transforming growth factor beta 1, thrombospondin 1, tenascin, and fibronectin. The presence of the epithelium enhanced the degree of tissue contraction (50.1 +/- 4.4% of original area versus 75.4 +/- 2.3%). In the absence of injury, tenascin, fibronectin, MMP-3, and tissue inhibitor of MMP-1 are actively expressed. However, the chronic chemical wound markedly inhibited the expression of all proteins. We conclude that the epithelium, wound type, and age of the tissue (contracting versus postcontraction) impact the expression of key proteins in an in vitro model of subepithelial fibrosis in asthma.
Agarwal
Angelie R
AR
Department of Chemical Engineering and Materials Science, 916 Engineering Tower, University of California, Irvine, Irvine, CA 92697-2575, USA.
Mih
Justin
J
George
Steven C
SC
D017209:Apoptosis / Q000502:physiology; D001249:Asthma / Q000150:complications / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis*; D006801:Humans; D007537:Isometric Contraction / Q000502:physiology; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D011658:Pulmonary Fibrosis / Q000150:complications / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D020545:Respiratory Mucosa / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012995:Solubility; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D053773:Transforming Growth Factor beta1; D014945:Wound Healing / Q000502:physiology
D016326:Extracellular Matrix Proteins; D012333:RNA, Messenger; C508960:TGFB1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9