title: Lung fibrotic tenascin-C upregulation is associated with other extracellular matrix proteins and induced by TGFβ1.
abstract: BACKGROUND
  Idiopathic 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.
  
  
  METHODS
  ECM 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.
  
  
  RESULTS
  A 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.
  
  
  CONCLUSIONS
  The 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.
authors: Susanna
authors: S
authors: Estany
authors: Vanesa
authors: V
authors: Vicens-Zygmunt
authors: Roger
authors: R
authors: Llatjós
authors: Ana
authors: A
authors: Montes
authors: Rosa
authors: R
authors: Penín
authors: Ignacio
authors: I
authors: Escobar
authors: Antoni
authors: A
authors: Xaubet
authors: Salud
authors: S
authors: Santos
authors: Frederic
authors: F
authors: Manresa
authors: Jordi
authors: J
authors: Dorca
authors: Respiratory Research Group, IDIBELL, University of Barcelona, Barcelona, Spain. mariamolinamolina@hotmail.com.
authors: Maria
authors: M
authors: Molina-Molina
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D000542:Alveolitis, Extrinsic Allergic / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D002908:Chronic Disease; D015536:Down-Regulation; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D008168:Lung / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D019063:Tenascin / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D015854:Up-Regulation; D053675:Versicans / Q000235:genetics / Q000378:metabolism
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D005353:Fibronectins; D012333:RNA, Messenger; D019063:Tenascin; D053773:Transforming Growth Factor beta1; D053675:Versicans