Source: Annual Congress 2002 - Interstitial lung disease
Disease area: Interstitial lung diseases

Abstract

Idiopathic pulmonary fibrosis (IPF) is a disorder of abnormal wound healing, resulting from ongoing epithelial damage, activation and repair, associated with discrete areas of myofibroblast activation and extracellular matrix (ECM) deposition. Mechanisms underlying these processes are poorly defined but seem to involve altered apoptosis of epithelial and myofibroblast cell types (Selman M et al. Ann. Intern. Med. 2001; 134: 136-151). Recent studies suggest that the profibrotic connective tissue growth factor (CTGF) acts downstream of, and in concert with, transforming growth factor (TGF)-β to drive fibrogenesis. In support, we previously reported CTGF overexpression in IPF (Allen JT et al. Am. J. Respir. Cell Mol. Biol. 1999; 21:693-700). In the present work we considered if CTGF modulates apoptosis of primary bronchial epithelial cells (NHBE) and IPF-derived primary lung fibroblasts (HIPF-1) cultured in-vitro. A specific CTGF-antisense oligonucleotide was used to block CTGF overexpression in these cells. Cells were treated with TGF-β (5ng/ml) to induce CTGF and co-incubated with either CTGF-antisense or CTGF-mismatch oligonucleotides (0-40μg/ml). Apoptosis was detected in cells by immunoassay of histone-bound DNA fragmentation and confirmed by anti-active caspase-3 immunocytochemistry. Data showed CTGF-dependent differential modulation of apoptosis, with an induction of NHBE cell apoptosis (by 60%, p<0.05) and suppression of HIPF-1 apoptosis (by 55%, p<0.05). Thus, an additional fibrogenic effect of CTGF in IPF may be to influence epithelial-mesenchymal interactions through selective modulation of apoptosis, inhibiting re-epithelialisation and disappearance of myofibroblasts, thereby favouring development of a fibrotic phenotype.

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Citations should be made in the following way:
J. T. Allen, E. Parker, M. A. Spiteri (Stoke-on-Trent, United Kingdom). Apoptosis of lung epithelial or fibroblast cell types is differentially modulated by CTGF. Eur Respir J 2002; 20: Suppl. 38, 3752

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