Open Access Highly Accessed Research article

Lung fibrotic tenascin-C upregulation is associated with other extracellular matrix proteins and induced by TGFβ1

Susanna Estany1, Vanesa Vicens-Zygmunt12, Roger Llatjós13, Ana Montes1, Rosa Penín3, Ignacio Escobar4, Antoni Xaubet56, Salud Santos12, Frederic Manresa12, Jordi Dorca126 and Maria Molina-Molina126*

Author Affiliations

1 Respiratory Research Group, IDIBELL, University of Barcelona, Barcelona, Spain

2 Unit of Interstitial Lung Diseases, Department of Respiratory Diseases, University Hospital of Bellvitge, Barcelona, Spain

3 Department of Pathology, University Hospital of Bellvitge, Barcelona, Spain

4 Department of Thoracic Surgery, University Hospital of Bellvitge, Barcelona, Spain

5 Department of Pulmonology, Hospital Clinic, Barcelona, Spain

6 CIBER, National Research Consortium CIBER of Respiratory Diseases (CIBERES), c. Feixa Llarga, s.n. 08907 L'Hospitalet de Llobregat, Barcelona, Spain

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BMC Pulmonary Medicine 2014, 14:120  doi:10.1186/1471-2466-14-120

Published: 26 July 2014

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.

Keywords:
Extracellular matrix; Idiopathic pulmonary fibrosis; Glycoproteins; Tenascin-C