Abstract
BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive parenchymal lung disease of unknown aetiology and poor prognosis, characterized by altered tissue repair and fibrosis. The extracellular matrix (ECM) is a critical component in regulating cellular homeostasis and appropriate wound healing. The aim of our study was to determine the expression profile of highlighted ECM proteins in IPF lungs.MethodsECM gene and protein expression was analyzed by cDNA microarrays, rt-PCR, immunohistochemistry and western-blot in lungs from idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis (HP), categorized as chronic (cHP) and subacute (saHP), and healthy lung tissue. Primary fibroblast cultures from normal subjects and fibrotic patients were studied to evaluate tenascin-C (TNC) synthesis.ResultsA total of 20 ECM proteins were upregulated and 6 proteins downregulated in IPF. TNC was almost undetected in normal lungs and significantly upregulated in fibrotic lungs (IPF and cHP) compared to saHP. Furthermore, it was located specifically in the fibroblastic foci areas of the fibrotic lung with a subepithelial gradient pattern. TNC levels were correlated with fibroblastic foci content in cHP lungs. Versican and fibronectin glycoproteins were associated with TNC, mainly in fibroblastic foci of fibrotic lungs. Fibroblasts from IPF patients constitutively synthesized higher levels of TNC than normal fibroblasts. TNC and α-sma was induced by TGF-β1 in both fibrotic and normal fibroblasts. TNC treatment of normal and fibrotic fibroblasts induced a non-significant increased α-sma mRNA.ConclusionsThe difference in ECM glycoprotein content in interstitial lung diseases could contribute to the development of lung fibrosis. The increase of TNC in interstitial areas of fibrotic activity could play a key role in the altered wound healing.
Highlights
Idiopathic pulmonary fibrosis (IPF) is a progressive parenchymal lung disease of unknown aetiology and poor prognosis, characterized by altered tissue repair and fibrosis
The IPF subjects showed the lowest value of forced vital capacity (FVC) (63% ± 14.6%) when compared with normal group (91.8% ± 2.4%, p < 0.001), chronic hypersensitivity pneumonitis (cHP) (68% ± 16%, p = 0.5) and subacute hypersensitivity pneumonitis (saHP) patients (72% ± 17.5%, p = 0.42)
The results of this study show that IPF lungs present a defined extracellular matrix (ECM) glycoprotein pattern that differs from inflammatory interstitial and normal lungs, but this protein profile is similar to other lung fibrotic disorders such as cHP
Summary
Idiopathic pulmonary fibrosis (IPF) is a progressive parenchymal lung disease of unknown aetiology and poor prognosis, characterized by altered tissue repair and fibrosis. The histological defined pattern is the usual interstitial pneumonia (UIP) characterized by the loss of epithelial structures, the appearance of interstitial fibrosis, microscopic honeycombing and focal areas of fibroblast-myofibroblast aggregates termed “fibroblastic foci”. These foci are associated with poor prognosis of disease and contain several hallmarks of the reactive stroma [2]. This stroma exhibits an excessive deposition of extracellular matrix (ECM) components, such us collagen I, collagen III and structural glycoproteins and proteoglycans. Other authors have described the association of TNC expression with the progression and aggression of cancer [7]
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