Abstract
Idiopathic pulmonary fibrosis (IPF) is a devastating and common chronic lung disease pathologically characterized by loss of epithelial cells and activation of fibroblasts and myofibroblasts. The etiology of IPF remains unclear and the disease pathology is poorly understood with no known efficacious therapy. PM014 is an herbal extract that has been shown to have beneficial effects in pulmonary diseases, which are likely to exert anti-inflammatory bioactions. In the present study, we observed that bleomycin (BLM) caused increased inflammatory infiltration as well as collagen deposition in lungs of mice on day 14 after treatment. Administration of PM014 suppressed BLM-induced inflammatory responses and fibrotic changes in dose-dependent manner in mice. Additionally, we provided in vitro evidence suggesting that PM014 inhibited TGF-β1-induced epithelial-mesenchymal transition (EMT) and fibroblast activation in alveolar epithelial cells and human lung fibroblasts from healthy donor and IPF patients. PM014 appeared to target TGF-β1 signaling via Smad-dependent pathways and p38 mitogen-activated protein kinases (MAPKs) pathways. Taken together, our data suggest that PM014 administration exerts a protective effect against lung fibrosis and highlight PM014 as a viable treatment option that may bring benefits to patient with IPF.
Highlights
Idiopathic pulmonary fibrosis (IPF) is a chronic and devastating lung disease of unknown etiology[1]
Mice treated with bleomycin displayed notable deposition of collagen, as indicated by semi-quantitative analysis using fibrotic Aschroft scoring (Fig. 1d) and quantitative histological collagen morphometry assessed by the fibrosis fraction (Fig. 1e) from Masson’s trichrome stained tissues, and biochemical collagen quantification determined by measuring hydroxyproline (Fig. 1f)
We demonstrated the potential utility of PM014 as a signaling pathway inhibitor that can block transforming growth factor (TGF)-β1 signaling by inactivating Smad-dependent and Smad-independent p38 mitogen-activated protein kinases (MAPKs) signaling in alveolar epithelial cells and lung fibroblasts
Summary
Idiopathic pulmonary fibrosis (IPF) is a chronic and devastating lung disease of unknown etiology[1]. Two drugs approved by the FDA, such as pirfenidone and nintedanib, have been considered promising therapeutic agents for slowing down the progression of the disease, mainly by changing forced vital capacity (FVC)[4,5] These drugs have some serious potential side effects and neither of these drugs have been found to effectively reverse lung fibrosis[5,6]. Considering the anti-inflammatory potential of PM014 in lung diseases, we hypothesize that PM014 protects against IPF To test this hypothesis, we induced lung fibrosis with bleomycin treatment on mice in vivo and induced EMT with TGF-β1 treatment on A549 cells as well as human lung fibroblasts (HLFs) in vitro. Our data indicate that a novel herbal extract PM014 could be therapeutic target for treatment of pulmonary fibrosis
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