Abstract
Idiopathic pulmonary fibrosis (IPF) is characterized by fibrotic change in alveolar epithelial cells and leads to the irreversible deterioration of pulmonary function. Transforming growth factor-beta 1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) in type 2 lung epithelial cells contributes to excessive collagen deposition and plays an important role in IPF. Atractylodin (ATL) is a kind of herbal medicine that has been proven to protect intestinal inflammation and attenuate acute lung injury. Our study aimed to determine whether EMT played a crucial role in the pathogenesis of pulmonary fibrosis and whether EMT can be utilized as a therapeutic target by ATL treatment to mitigate IPF. To address this topic, we took two steps to investigate: 1. Utilization of anin vitro EMT model by treating alveolar epithelial cells (A549 cells) with TGF-β1 followed by ATL treatment for elucidating the underlying pathways, including Smad2/3 hyperphosphorylation, mitogen-activated protein kinase (MAPK) pathway overexpression, Snail and Slug upregulation, and loss of E-cadherin. Utilization of an in vivo lung injury model by treating bleomycin on mice followed by ATL treatment to demonstrate the therapeutic effectiveness, such as, less collagen deposition and lower E-cadherin expression. In conclusion, ATL attenuates TGF-β1-induced EMT in A549 cells and bleomycin-induced pulmonary fibrosis in mice.
Highlights
Idiopathic pulmonary fibrosis (IPF) is considered a chronic inflammatory disorder that gradually progresses to irreversible lung tissue fibrosis [1]
We propose the safe dosage of atractylodin and confirm the anti-epithelial-mesenchymal transition (EMT) pathway via inhibiting TGF-β1/Smad and mitogen-activated protein kinase (MAPK) signaling cascades in human alveolar epithelial A549 cells and in mice
These results indicate that atractylodin and TGF-β1 induced no cytotoxicity within the concentrations we tested and that atractylodin could potentially
Summary
Idiopathic pulmonary fibrosis (IPF) is considered a chronic inflammatory disorder that gradually progresses to irreversible lung tissue fibrosis [1]. The cause of IPF is uncertain, and the clinical course is unpredictable. It has a poor prognosis with median survival of. The major characteristics of IPF are alveolar structure damage and flourishing extracellular matrix (ECM) deposition in the basement membrane and interstitial tissue [3]. The possible mechanisms include abnormal fibroblast proliferation and transformation, myofibroblast phenoconversion, and epithelial mesenchymal transition [4,5]. Recruited fibroblasts begin to produce and deposit large amounts of ECM proteins, including collagen type I and III [6]. Myofibroblasts, α-smooth muscle actin (α-SMA)-expressing fibroblasts, even possess a greater ability to produce type I collagen than fibroblasts [7]. In 2014, the U.S Food and Drug Administration (FDA) recognized
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