Background: Idiopathic pulmonary fibrosis (IPF) is a progressive parenchymal lung disease of unknown aetiology\nand poor prognosis, characterized by altered tissue repair and fibrosis. The extracellular matrix (ECM) is a critical\ncomponent in regulating cellular homeostasis and appropriate wound healing. The aim of our study was to\ndetermine the expression profile of highlighted ECM proteins in IPF lungs.\nMethods: ECM gene and protein expression was analyzed by cDNA microarrays, rt-PCR, immunohistochemistry and\nwestern-blot in lungs from idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis (HP), categorized as\nchronic (cHP) and subacute (saHP), and healthy lung tissue. Primary fibroblast cultures from normal subjects and\nfibrotic patients were studied to evaluate tenascin-C (TNC) synthesis.\nResults: A total of 20 ECM proteins were upregulated and 6 proteins downregulated in IPF. TNC was almost\nundetected in normal lungs and significantly upregulated in fibrotic lungs (IPF and cHP) compared to saHP.\nFurthermore, it was located specifically in the fibroblastic foci areas of the fibrotic lung with a subepithelial gradient\npattern. TNC levels were correlated with fibroblastic foci content in cHP lungs. Versican and fibronectin\nglycoproteins were associated with TNC, mainly in fibroblastic foci of fibrotic lungs. Fibroblasts from IPF patients\nconstitutively synthesized higher levels of TNC than normal fibroblasts. TNC and ?-sma was induced by TGF-?1 in\nboth fibrotic and normal fibroblasts. TNC treatment of normal and fibrotic fibroblasts induced a non-significant\nincreased ?-sma mRNA.\nConclusions: The difference in ECM glycoprotein content in interstitial lung diseases could contribute to the\ndevelopment of lung fibrosis. The increase of TNC in interstitial areas of fibrotic activity could play a key role in\nthe altered wound healing.
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