Abstract
Introduction: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic interstitial lung disease of uncertain etiology. It has been recently hypothesized that IPF is considered a neoproliferative disorder of lung. Activated fibroblasts are the central effector cells of the progressive fibrotic process in IPF. This study was aimed to investigate whether IPF lung fibroblasts activation is regulated by PTEN in vitro.
Methods: Lung tissues were obtained from patients with histologic confirmed IPF and primary spontaneous pneumothorax. Primary fibrotic and normal human lung fibroblasts were isolated. Immunohistochemistry staining was used to locate PTEN and a-SMA in lung tissue and Western blot was used for the expression of PTEN in fibroblasts. The function of PTEN in fibroblast activation was evaluated using human fetal lung fibroblast (MRC-5) with down-regulated PTEN by siRNA.
Result: Compared normal controls, fibroblasts within fibrotic foci demonstrated diminished PTEN expression by immunohistochemistry staining in lung tissue from patients with IPF. PTEN expression was decreased in fibroblasts isolated from IPF by Western blot. While knockdown of PTEN by siRNA in MRC-5 cells, a-SMA and collagen I expression were both up-regulated by immunofluorescent confocal microscopic and western blot analysis. Meanwhile cell proliferation and migration were promoted and the ability of apoptosis-resistant was increased.
Conclusion: These findings indicate that lung fibroblasts have decreased PTEN expression in IPF. Inhibition of PTEN induced fibroblast activation and exhibiting similar pathogenic features to cancer cells.
- © 2014 ERS