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Abstract
Context: Previous studies have reported that caveolin-1 (Cav-1) is associated with lung fibrosis. However, the role of Cav-1 expression in pirfenidone-treated idiopathic pulmonary fibrosis (IPF) is unknown. Objective: This study investigated Cav-1 expression in pirfenidone-treated IPF, and compared the effects of pirfenidone with acetylcysteine and prednisone on IPF. Materials and methods: Rat IPF model was established by endotracheal injection of 5 mg/kg bleomycin A5 into the specific pathogen-free Wistar male rats. Pirfenidone (P, 100 mg/kg once daily), prednisone (H, 5 mg/kg once daily) and acetylcysteine (N, 4 mg/kg 3 times per day) were used to treat the rat model by intragastric administration for 45 consecutive days, respectively. The normal rats without IPF were used as the controls. After 15, 30 and 45 days of drug treatment, lung histopathology was assessed. The expression of Cav-1 was determined using real-time quantitative PCR and Western blot; the expression of tumour necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1) and platelet-derived growth factor (PDGF) was determined by enzyme-linked immunosorbent assay. Results: After 15, 30 and 45 days of drug treatment, comparison of the three drug-treated groups with the model group showed significantly lower (p < 0.05) significance of airsacculitis and fibrosis scores of lung tissues, as well as expression of TGF-β1, TNF-α and PDGF, but the expression of Cav-1 was higher (p < 0.05). Compared with the N group, the fibrosis score was significantly lower and the protein expression of Cav-1 was significantly higher in the P group (p < 0.05). Additionally, the expression of Cav-1 was negatively correlated with the airsacculitis and fibrosis scores (r = −0.506, p < 0.01; r = -0.676, p < 0.01) as well as expression of TGF-β1, TNF-α and PDGF (r = −0.590, p < 0.01; r = −0.530, p < 0.01; r = −0.553, p < 0.01). Discussion and conclusion: Pirfenidone, prednisone and acetylcysteine can inhibit airsacculitis and pulmonary fibrosis in rat IPF models, which may be related with enhanced caveolin-1, reduced TNF-α, TGF-β1, PDGF.
Highlights
Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial pneumonia and characterized by extracellular matrix (ECM) remodelling and abnormal proliferation of fibroblasts in pulmonary parenchyma (Thannickal et al 2004; Prasse 2015)
Rat IPF model was established by endotracheal injection of bleomycin A5 in order to investigate the role of Cav-1 expression in IPF after pirfenidone, acetylcysteine and prednisone treatments, and compare the effects of pirfenidone with acetylcysteine and prednisone on IPF
According to HE staining, both airsacculitis score and fibrosis score of lung tissues in the P, H and N groups were significantly lower than those in the M group at the three time points (p < 0.05), indicating that pirfenidone, acetylcysteine and prednisone were able to alleviate the symptoms of airsacculitis and fibrosis of IPF
Summary
Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial pneumonia and characterized by extracellular matrix (ECM) remodelling and abnormal proliferation of fibroblasts in pulmonary parenchyma (Thannickal et al 2004; Prasse 2015). The pathogenesis of pulmonary fibrosis has not been clearly uncovered, but various cytokines and other molecules have been discovered to play crucial roles in the progression of pulmonary fibrosis, such as tumour necrosis factor-a (TNF-a) (Pantelidis et al 2001), transforming growth factor-b1 (TGF-b1) (Willis et al 2005), platelet-derived growth factor (PDGF) (Antoniades et al 1990) and caveolin-1 (Cav-1) (Shivshankar et al 2012). There is evidence that alterations of Cav-1 function lead to ECM production in fibroblasts and are associated with lung fibrosis (Wang et al 2006; Xia et al 2010). Cav-1 is able to inhibit the expression of TGF-b1 and PDGF (Yamamoto et al 1999; Razani et al 2001), and regulate TNF-a-induced endothelial cell activation and inflammation (Wang et al 2008). In IPF, the relationships of Cav-1 expression and these cytokines are still unknown
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