Effect of the Wnt1/β-catenin signalling pathway on human embryonic pulmonary fibroblasts.

Abstract

Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease associated with a high rate of mortality, characterised by an accumulation of fibroblasts/myofibroblasts in the fibroblastic foci (FF) and by an excessive deposition of extracellular matrix (ECM) in the lung parenchyma. The pathogenesis of this fatal disorder remains unclear. Previous evidence suggests that myofibroblasts are key effectors of the deposition of ECM. In the present study, human embryonic pulmonary fibroblast (HEPF) cells were incubated with different concentrations of Wnt1. The present study revealed that cell proliferation improved following stimulation using different concentrations of Wnt1 in a concentration-dependent manner. When the concentration exceeded 20µg/l, cell proliferation was significant (P<0.05) and the cell expression of α-SMA, vimentin and collagen I mRNA, as well as protein expression, significantly increased (P<0.05). Bronchoalveolar lavage fluid (BALF) was then obtained from bleomycin (BLM)-induced models of pulmonary fibrosis. HEPF cells were cultured with Dulbecco's modified Eagle's medium plus BALF. The mRNA and protein expression of α-SMA, vimentin and collagen I significantly increased and these increases were associated with β-catenin. Furthermore, following being infected with the lentivirus expressing β-catenin shRNA, HEPF cells were cultured with BALF. However, the mRNA and protein expression of α-SMA, vimentin and collagen I did not increase significantly. The present study suggested that the Wnt1/β-catenin signalling pathway can promote HEPF cell proliferation and induced HEPF cells can change into myofibroblasts and promote ECM deposition. These findings may provide a theoretical basis for the treatment of IPF.