Abstract
BackgroundNeurotrophins (NT) belongs to a family of growth factors which promotes neurons survival and differentiation. Increasing evidence show that NT and their receptor are expressed in lung tissues suggesting a possible role in lung health and disease. Here we investigated the expression and functional role of the TrkB/BDNF axis in idiopathic pulmonary fibrotic lung (myo)fibroblasts.MethodsLung fibroblast were isolated from IPF patients and characterized for the expression of mesenchymal markers in comparison to normal lung fibroblasts isolated from non-IPF controls.ResultsBDNF treatment promoted mesenchymal differentiation and this effect was counteracted by the TrkB inhibitor K252a. In this regard, we showed that K252a treatment was able to control the expression of transcription factors involved in epithelial to mesenchymal transition (EMT). Accordingly, K252a treatment reduced matrix metalloproteinase-9 enzyme activity and E-cadherin expression while increased cytoplasmic β-catenin expression.ConclusionsOur results suggest that BDNF/TrkB axis plays a role in EMT promoting the acquisition of (myo)fibroblast cell phenotype in IPF. Targeting BDNF/TrkB seems to represent a viable approach in order to prevent EMT dependent lung fibrosis.
Highlights
Neurotrophins (NT) belongs to a family of growth factors which promotes neurons survival and differentiation
Lung fibroblast from human Idiopathic pulmonary fibrosis (IPF) show higher levels of epithelial-to-mesenchymal transition (EMT) Human primary cell lines of fibroblast derived from either normal and IPF lungs were assessed for EMT markers using flow cytometry
We observed that approximately 35% of our cultured fibroblasts derived from IPF lung expressed N-cadherin where almost all of them 99% were positive for vimentin
Summary
Neurotrophins (NT) belongs to a family of growth factors which promotes neurons survival and differentiation. We investigated the expression and functional role of the TrkB/BDNF axis in idiopathic pulmonary fibrotic lung (myo)fibroblasts. Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease characterized by fibroblast accumulation, collagen deposition, and parenchyma destruction [1, 2]. Despite (myo) fibroblasts seem to play a critical role in this process, their origin within the lung is still controversial. EMT is a molecular process by which epithelial cells trans-differentiate into motile mesenchymal cells. It contributes pathologically to fibrosis and cancer progression [10]. This phenomenon is mediated by specific transcription molecules like Twist and Snail (1 and 2-Slug-) that activate the EMT during the development of fibrosis and cancer [11]
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