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EMT and pulmonary fibrosis

Shencun Fang, Huifang Guo, Yusi Cheng, Zewei Zhou, Wei Zhang, Bing Han, Wei Luo, Jing Wang, Weiping Xie, Jie Chao
Excessive proliferation and migration of fibroblasts contribute to pulmonary fibrosis in silicosis, and both epithelial cells and endothelial cells participate in the accumulation of fibroblasts via the epithelial-mesenchymal transition (EMT) and the endothelial-mesenchymal transition (EndMT), respectively. A mouse endothelial cell line (MML1) was exposed to silicon dioxide (SiO2 , 50 μg/cm2 ), and immunofluorescence and western blot analyses were performed to evaluate levels of specific endothelial and mesenchymal markers and to elucidate the mechanisms by which SiO2 induces the EndMT...
March 14, 2018: Cell Death & Disease
Yangyang Gu, Bo Huang, Yanfei Yang, Mengdie Qi, Guohua Lu, Dajing Xia, Hequan Li
Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible lung disease with high mortality rate. The etiology is unknown and treatment choices are limited. Thus, there is great interest to investigate novel agents for IPF therapy. Ibrutinib, BTK, and ITK irreversible inhibitor is a FDA-approved small molecule for the clinical therapy of B cell lymphoma. Its role in pulmonary fibrosis remains unknown. In this study, we investigated the anti-fibrotic activity of ibrutinib. Strikingly, ibrutinib did not inhibit but exacerbated bleomycin-induced pulmonary fibrosis by increased epithelial cell apoptosis, and inflammation in the lung...
March 13, 2018: Inflammation
Dong Weng, Jian-Xia Chen, Hao-Hao Li, Feng Liu, Li-Dan Zhou, Hai-Peng Liu, Rui-Juan Zheng, Yan Jiang, Zhong-Hua Liu, Baoxue Ge
The epithelial-mesenchymal transition (EMT) is a multifunctional cell process involved in the pathogenesis of numerous conditions, including fibrosis and cancer. Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease characterized by fibroblast accumulation and collagen deposition in the lungs. The fibroblasts involved in this process partially originate from lung epithelial cells via the EMT. Evidence suggests that the EMT contributes to progression, invasion, and metastasis of various types of cancer...
December 2018: Cell Death Discovery
Ana Valero-Jiménez, Joaquín Zúñiga, José Cisneros, Carina Becerril, Alfonso Salgado, Marco Checa, Ivette Buendía-Roldán, Criselda Mendoza-Milla, Miguel Gaxiola, Annie Pardo, Moisés Selman
Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease characterized by epithelial cell activation, expansion of the fibroblast population and excessive extracellular matrix accumulation. The mechanisms are incompletely understood but evidence indicates that the deregulation of several proteases contributes to its pathogenesis. Transmembrane protease serine 4 (TMPRSS4) is a novel type II transmembrane serine protease that may promote migration and facilitate epithelial to mesenchymal transition (EMT), two critical processes in the pathogenesis of IPF...
2018: PloS One
Xianhua Gui, Lingyun Sun, Luo Gu, Hourong Cai, Hongwei Chen
Leptin, a protein-related product of the obesity gene, plays an important role in the pathogenesis of fibrotic diseases including pulmonary fibrosis. As a highly conservative process, autophagy regulates various biological functions. Otherwise, insufficient autophagy has been described in alveolar epithelial cells (AEC) to cope with the progression of pulmonary fibrosis. Hence, this study is to investigate the effects of leptin on fibrosis in TGF-β1 induced epithelial mesenchymal transition (EMT) and the potential roles of autophagy in this processes...
March 7, 2018: Biochemical and Biophysical Research Communications
Jian Lu, Yongbing Qian, Wei Jin, Rui Tian, Yong Zhu, Jinfeng Wang, Xiaoxiao Meng, Ruilan Wang
Pulmonary fibrosis (PF) is one of the most prevalent causes of death following paraquat (PQ) poisoning. As demonstrated in previous studies by the present authors, epithelial-to-mesenchymal transition (EMT) is associated with PQ-induced PF. In addition, hypoxia-inducible factor-1α (HIF-1α) and lysyl oxidase (LOX) promote EMT following PQ poisoning. However, the association between HIF-1α- and LOX-mediated regulation of EMT remains unclear. The present study investigated the association between HIF-1α and LOX with regard to PQ-induced EMT...
March 2018: Experimental and Therapeutic Medicine
Masashi Kawami, Rika Harabayashi, Risako Harada, Yohei Yamagami, Ryoko Yumoto, Mikihisa Takano
Methotrexate (MTX) often induces serious lung diseases such as pulmonary fibrosis. Although MTX is known to be a folic acid (FA) antagonist, the effect of FA on MTX-induced lung injury remains unclear. Recent studies indicate that epithelial-mesenchymal transition (EMT) is involved in pulmonary fibrosis. Here, we aimed to clarify the effect of FA on MTX-induced EMT in human alveolar epithelial cell line A549 using conditioned medium (CM). CM was prepared from the supernatants of A549 cells treated with MTX in the absence (CMM) or presence (CMMF) of FA...
February 12, 2018: Biochemical and Biophysical Research Communications
Liyan Wu, Zujin Luo, Jinxu Zheng, Peng Yao, Zhenyan Yuan, Xiaohong Lv, Jing Zhao, Min Wang
IL-33 played an important role in inflammatory diseases as evidenced by their high levels of expression in diseased tissues. Previous studies showed that IL-33/ST2L signal transduction pathway participated in epithelial-mesenchymal transition (EMT) of A549 cells. Cytokine IL-1β can increase the expression of MMPs by activating NF-kB. The excessive or inappropriate expression of MMP-9 may randomly and non-selectively destroy the extracellular matrix. TIMP-1 (tissue inhibitor of MMP-9) effects on ebb and flow of ECM by inhibiting activation of MMP-9...
February 7, 2018: Inflammation
S N Sunilgowda, Devipriya Nagarajan, Devipriya Nagarajan
Radiotherapy is the most widely used treatment method for average and advanced lung cancer patients. Moreover, the clinical toxicities caused by radiotherapy are categorized into acute radiation pneumonitis and late pulmonary fibrosis. Epithelial-mesenchymal transition (EMT) is a complex physiological process involves many signaling molecules and proteins like adaptor proteins, and transcriptional factors. It was identified as a significant mechanism for fibrosis, wound healing and also cancer. A variety of biomarkers have appeared in radiation-induced lung EMT, some of which are acquired (N-cadherin, vimentin and fibronectin, etc...
February 6, 2018: Current Drug Targets
Thomas Divya, Bakthavatchalam Velavan, Ganapasam Sudhandiran
The respiratory disease pulmonary fibrosis (PF), which is characterized by scar formation throughout the lung, imposes a serious health burden. No effective drug without side effects has been proven to prevent this fatal lung disease. In this context, the present study was undertaken to elucidate the protective effect of celastrol, a quinine methide pentacyclic triterpenoid from a Chinese medicinal plant 'thunder God vine' against bleomycin (BLM)-induced PF. We also attempted to study how the cytokine transforming growth factor-β (TGF-β) stimulates fibrosis through the induction of epithelial-mesenchymal transition (EMT) and the role of celastrol in regulating EMT...
February 2, 2018: Basic & Clinical Pharmacology & Toxicology
Mariel Maldonado, Alfonso Salgado-Aguayo, Iliana Herrera, Sandra Cabrera, Blanca Ortíz-Quintero, Claudia A Staab-Weijnitz, Oliver Eickelberg, Remedios Ramírez, Anne M Manicone, Moisés Selman, Annie Pardo
Idiopathic Pulmonary Fibrosis (IPF) is a chronic and progressive aging-associated disease of unknown etiology. Growing body of evidence indicates that aberrant activated alveolar epithelial cells induce the expansion and activation of the fibroblast population leading to the destruction of the lung architecture. Some Matrix Metalloproteinases (MMPs) are upregulated in IPF, indicating that they may be important in the pathogenesis and/or progression of IPF. Here, we studied the expression of MMP28 in this disease and evaluated its functional effects in two alveolar epithelial cell lines and in human primary bronchial epithelial cells...
January 26, 2018: American Journal of Respiratory Cell and Molecular Biology
Zhihui Zhang, Jiao Qu, Cheng Zheng, Panpan Zhang, Wencheng Zhou, Wenhui Cui, Xiaoting Mo, Liucheng Li, Liang Xu, Jian Gao
Epithelial mesenchymal transition (EMT) is a key progression that promotes pulmonary fibrosis (PF). Numb, a phosphotyrosine-binding domain (PTB) protein, is implicated with EMT. Nuclear factor erythroid 2-related factor2 (Nrf2) and its downstream proteins heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) constitute an important pathway of antioxidant defense signal for protecting against PF. It remains elusive whether Nrf2 antioxidant pathway and Numb have a potential relationship in EMT-mediated PF...
January 23, 2018: Cell Death & Disease
Da Young Shin, Mi Ho Jeong, In Jae Bang, Ha Ryong Kim, Kyu Hyuck Chung
Polyhexamethylene guanidine phosphate (PHMG-phosphate), an active component of humidifier disinfectant, is suspected to be a major cause of pulmonary fibrosis. Fibrosis, induced by recurrent epithelial damage, is significantly affected by epigenetic regulation, including microRNAs (miRNAs). The aim of this study was to investigate the fibrogenic mechanisms of PHMG-phosphate through the profiling of miRNAs and their target genes. A549 cells were treated with 0.75 μg/mL PHMG-phosphate for 24 and 48 h and miRNA microarray expression analysis was conducted...
January 11, 2018: Toxicology Letters
Sheng-Lan Tian, Yang Yang, Xiao-Liu Liu, Qing-Bang Xu
BACKGROUND Idiopathic pulmonary fibrosis (IPF) can severely damage lung function, which may result in death. Emodin is a major ingredient of rhubarb and has been proven to protect against lung disruptions. Our study focused on the potential medicinal effect of emodin against IPF. MATERIAL AND METHODS The experiment subjects were fully-grown male Sprague-Dawley rats with average weight of 180-220 kg. Histological analyses, Western blotting analysis, quantitative real-time PCR, and statistical analysis were used in the study...
January 1, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Xiang Li, Xiaopei Yan, Yanli Wang, Jingjing Wang, Fang Zhou, Hong Wang, Weiping Xie, Hui Kong
Silicosis is an incurable and progressive lung disease characterized by chronic inflammation and fibroblasts accumulation. Studies have indicated a vital role for epithelial-mesenchymal transition (EMT) in fibroblasts accumulation. NLRP3 inflammasome is a critical mediator of inflammation in response to a wide range of stimuli (including silica particles), and plays an important role in many respiratory diseases. However, whether NLRP3 inflammasome regulates silica-induced EMT remains unknown. Our results showed that silica induced EMT in human bronchial epithelial cells (16HBE cells) in a dose- and time-dependent manner...
December 16, 2017: Experimental Cell Research
Xin Wang, Jun-Ling Gao, Man-Man Zhao, Hui-Xing Zhu, Yan-Xia Tian, Ran Li, Xiao-Hua Jiang, Lei Yu, Jing-Rui Tian, Jian-Zhong Cui
Pulmonary fibrosis (PF) is a chronic lung disease. The transforming growth factor-β1 (TGF-β1)/Smad3 signaling pathway plays an important role in the pathogenesis of pulmonary fibrosis. Bone marrow-derived mesenchymal stem cells (BMSCs) have been shown to be a modulator of the molecular aspects of the fibrosis pathway. However, it is still unknown as to whether the conditioned medium from BMSCs (BMSCs-CM) inhibits the epithelial-mesenchymal transition (EMT) process. This study confirmed the hypothesis that BMSCs-CM exerts an anti-fibrotic effect on human type II alveolar epithelial cells (A549) by suppressing the phosphorylation of Smad3...
February 2018: International Journal of Molecular Medicine
Hong Chen, Qun Chen, Chun-Ming Jiang, Guang-Yue Shi, Bo-Wen Sui, Wei Zhang, Li-Zhen Yang, Zhu-Ying Li, Li Liu, Yu-Ming Su, Wen-Cheng Zhao, Hong-Qiang Sun, Zhen-Zi Li, Zhou Fu
Idiopathic pulmonary fibrosis (IPF) and tumor are highly similar to abnormal cell proliferation that damages the body. This malignant cell evolution in a stressful environment closely resembles that of epithelial-mesenchymal transition (EMT). As a popular EMT-inducing factor, TGFβ plays an important role in the progression of multiple diseases. However, the drugs that target TGFB1 are limited. In this study, we found that triptolide (TPL), a Chinese medicine extract, exerts an anti-lung fibrosis effect by inhibiting the EMT of lung epithelial cells...
March 1, 2018: Toxicology Letters
Lianjun Lin, Qian Han, Yan Xiong, Ting Li, Zhonghui Liu, Huiying Xu, Yanping Wu, Nanping Wang, Xinmin Liu
Epithelial-mesenchymal transition (EMT) plays an important role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Krüpple-like-factor 4 (KLF4), has been suggested to play an important role in the phenotype transition. However, its function in pulmonary fibrosis and EMT of human alveolar epithelial cells (AECs) remains unclear. This study aimed to examine the role of KLF4 in pulmonary fibrosis and EMT. Decreased expression of KLF4 was first observed in human IPF lung tissues and models of bleomycin-induced pulmonary fibrosis...
November 20, 2017: Scientific Reports
Chun-Yan Li, Ya-Hong Wang, Zi-Ying Lin, La-Wei Yang, Sheng-Lan Gao, Tie Liu, Bao-An Zou, Zhan-Chun Pan, Ze-Qing Song, Gang Liu
Idiopathic pulmonary fibrosis (IPF) is a devastating disease and the pathogenesis of IPF remains unclear. Our previous study indicated that miR-5100 promotes the proliferation and metastasis of lung epithelial cells. In this study, we investigated the effect and mechanism of miR-5100 on bleomycin (BLM)-induced mouse lung fibrosis and transforming growth factor β (TGF-β1) or epidermal growth factor (EGF) induced EMT-model in A549 and Beas-2B cells. The elevated level of miR-5100 was observed in both the mouse lung fibrosis tissues and EMT cell model...
2017: American Journal of Translational Research
Xian-Long Zhou, Peng Xu, Hai-Hua Chen, Yan Zhao, Jun Shen, Cheng Jiang, Shan Jiang, Shao-Zhou Ni, Bing Xu, Lei Li
Recent evidence indicates that the epithelial to mesenchymal transition (EMT) in primary alveolar cells (AECs) plays an important role in idiopathic pulmonary fibrosis (IPF). In vivo models have suggested that thalidomide (THL) has anti-fibrotic effects against pulmonary fibrosis, but the underlying mechanism of this effect is not clear. This study investigated whether THL regulates alveolar EMT and the possible mechanisms underlying this process. CCL-149 cells were treated with TGF-β1 in the presence of THL at the indicated concentrations...
November 7, 2017: Scientific Reports
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