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Received Aug 18, 2017; Revised Oct 24, 2017; Accepted Nov 26, 2017
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1. Introduction
Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease with high lethality, a fatal prognosis, and a lack of effective medical therapies [1, 2]. The pathological characteristics of IPF mainly include the disruption of the pulmonary parenchymal matrix and replacement with fibrotic tissues [3, 4]. The development of IPF results in declining lung function and eventual respiratory failure, with a median survival of only 2-3 years following diagnosis [5]. Traditional drugs only have marginal effects against this disease [6]. Details of the mechanisms involved in IPF are also not well established, and there is an extreme lack of effective therapies for IPF.
One possible mechanism involved in IPF is the activation of α-smooth muscle actin (α-SMA). Higher expression of α-SMA is accompanied by more collagen deposition, indicating more severe pulmonary fibrosis (PF) [7]. Understanding the mechanism responsible for α-SMA activation is a potential way to determine the fibrotic pathogenesis. High-mobility group box 1 (HMGB1) is a highly conserved DNA-shepherding protein, which could translocate to the cytoplasm as well as the extracellular space during cell activation, injury, or death [8]. It has been demonstrated that HMGB1 could promote the expression of α-SMA in fibrotic diseases [9]. The detailed mode of action between HMGB1 and α-SMA in pulmonary fibrosis, however, has not yet been fully interpreted. Another mechanism involved in pulmonary fibrosis is the activation of the epidermal growth factor receptor (EGFR). EGFR has been found to be upregulated in the lung tissues of patients and rodents with pulmonary fibrosis [10–12]. Gefitinib, an EGFR-tyrosine kinase inhibitor (EGFR-TKI), has the ability to inhibit fibroblast proliferation, therefore lessening the collagen and extracellular matrix (ECM) deposition in pulmonary fibrosis [13, 14]. However, the concrete mechanism behind this inhibition has not yet been clearly determined. Oxidative stress is another key pathological process in the development of pulmonary fibrosis [15]. Previous studies have shown that bleomycin administration could increase oxidative stress by increasing the production of nitric-oxide synthase and NADPH...