Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and an irreversible lung disorder characterized by the accumulation of fibroblasts and myofibroblasts in the extracellular matrix. The transforming growth factor-β1 (TGF-β1)-induced epithelial-to-mesenchymal transition (EMT) is thought to be one of the possible sources for a substantial increase in the number of fibroblasts/myofibroblasts in IPF lungs. Tannic acid (TA), a natural dietary polyphenolic compound has been shown to possess diverse pharmacological effects. However, whether TA can inhibit TGF-β1-mediated EMT in lung epithelial cells remains enigmatic. Both the human adenocarcinomic alveolar epithelial (A549) and normal bronchial epithelial (BEAS-2B) cells were treated with TGF-β1 with or without TA. Results showed that TA addition, markedly inhibited TGF-β1-induced EMT as assessed by reduced expression of N-cadherin, type-1-collagen, fibronectin, and vimentin. Furthermore, TA inhibited TGF-β1-induced cell proliferation through inducing cell cycle arrest at G0/G1 phase. TGF-β1-induced increase in the phosphorylation of Smad (Smad2 and 3), Akt as well as that of mitogen activated protein kinase (ERK1/2, JNK1/2, and p38) mediators was effectively inhibited by TA. On the other hand, TA reduced the TGF-β1-induced increase in TGF-β receptors expression. Using molecular docking approach, FTIR, HPLC and Western blot analyses, we further identified the direct binding of TA to TGF-β1. Finally, we conclude that TA might directly interact with TGF-β1, thereby repressing TGF-β signaling and subsequent EMT process in lung epithelial cells. Further animal studies are needed to clarify its potential therapeutic benefit in pulmonary fibrosis.
Lack of markers of subclinical disease state and clinical phenotype other than pulmonary function test has made the diagnosis and interventions of environmental respiratory diseases a major challenge. MicroRNAs (miRNAs), small non-coding single stranded RNAs, have emerged as potential disease-modifier in various environmental respiratory diseases. They can also be found in various body fluids and are remarkably stable. Because of their high stability, disease-specific expression, and the ease to detect and quantify them have raised the potential of miRNAs in body fluids to be useful clinical diagnostic biomarkers for lung disease phenotyping. In the present review, we provide a comprehensive overview of progress made in identifying miRNAs in various body fluids including blood, serum, plasma, bronchoalveolar lavage (BAL) fluid, and sputum as biomarkers for a wide range of human respiratory diseases such as acute lung injury/acute respiratory distress syndrome (ALI/ARDS), idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), and asthma. Finally, we discuss several challenges remain to be concerned and suggest few disease-specific and non-specific miRNAs to become part of future clinical practice.
The overall data suggested that C-PC suppresses TGF- β1-induced EMT and warrants further in vivo studies for future evaluation of C-PC as a potential antifibrotic agent.
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