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EMT and pulmonary fibrosis

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https://www.readbyqxmd.com/read/28624451/rapamycin-protects-against-paraquat-induced-pulmonary-fibrosis-activation-of-nrf2-signaling-pathway
#1
Yiheng Xu, Wenlin Tai, Xiaoyuan Qu, Wenjuan Wu, ZhenKun Li, Shuhao Deng, Chanthasone Vongphouttha, Zhaoxing Dong
Paraquat (PQ) is a widely used herbicide indeveloping countries worldwide, and pulmonary fibrosis is one of the most typical features of PQ poisoning. The molecular mechanism of PQ toxicity especially how to treat PQ-induced pulmonary fibrosis is still largely unknown. In animal model of pulmonary fibrosis, we used HE staining, western blotting assay and Real-time PCR assay to analyze the effects of rapamycin on the PQ-induced epithelial mesenchymal transition (EMT). We found that PQ induced the pulmonary fibrosis using HE staining and Masson's staining, and up-regulated the activity of HYP and the mRNA expressions of Collagen I and III (COL-1and COL-3) in pulmonary tissues...
June 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28598023/nintedanib-reduces-ventilation-augmented-bleomycin-induced-epithelial-mesenchymal-transition-and-lung-fibrosis-through-suppression-of-the-src-pathway
#2
Li-Fu Li, Kuo-Chin Kao, Yung-Yang Liu, Chang-Wei Lin, Ning-Hung Chen, Chung-Shu Lee, Chih-Wei Wang, Cheng-Ta Yang
Mechanical ventilation (MV) used in patients with acute respiratory distress syndrome (ARDS) can increase lung inflammation and pulmonary fibrogenesis. Src is crucial in mediating the transforming growth factor (TGF)-β1-induced epithelial-mesenchymal transition (EMT) during the fibroproliferative phase of ARDS. Nintedanib, a multitargeted tyrosine kinase inhibitor that directly blocks Src, has been approved for the treatment of idiopathic pulmonary fibrosis. The mechanisms regulating interactions among MV, EMT and Src remain unclear...
June 9, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28591554/nlrp3-participates-in-the-regulation-of-emt-in-bleomycin-induced-pulmonary-fibrosis
#3
Rui Tian, Yong Zhu, Jiayi Yao, Xiaoxiao Meng, Jinfeng Wang, Hui Xie, Ruilan Wang
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and irreversible lung disease. Studies have shown that epithelial-mesenchymal transition (EMT) plays an important role in the development of IPF. The NLRP3 inflammasome is reported to be activated and play an important role in many respiratory diseases. However, whether the NLRP3 inflammasome is activated in alveolar epithelial cells as well as the regulatory role of NLRP3 in EMT have not been reported. In this study, we transfected NLRP3 siRNA into A549 and RLE-6TN cells and treated them with bleomycin (BLM) for 24h...
June 4, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28588349/distinct-roles-of-wnt-%C3%AE-catenin-signaling-in-the-pathogenesis-of-chronic-obstructive-pulmonary-disease-and-idiopathic-pulmonary-fibrosis
#4
REVIEW
Juan Shi, Feng Li, Meihui Luo, Jun Wei, Xiaoming Liu
Wnt signaling pathways are tightly controlled under a physiological condition, under which they play key roles in many biological functions, including cell fate specification and tissue regeneration. Increasing lines of evidence recently demonstrated that a dysregulated activation of Wnt signaling, particularly the Wnt/β-catenin signaling, was involved in the pathogenesis of chronic pulmonary diseases, such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). In this respect, Wnt signaling interacts with other cellular signaling pathways to regulate the initiation and pathogenic procedures of airway inflammation and remodeling, pulmonary myofibroblast proliferation, epithelial-to-mesenchymal transition (EMT), and development of emphysema...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28540808/exposure-to-febrile-range-hyperthermia-potentiates-wnt-signalling-and-epithelial-mesenchymal-transition-gene-expression-in-lung-epithelium
#5
Ratnakar Potla, Mohan E Tulapurkar, Irina G Luzina, Sergei P Atamas, Ishwar S Singh, Jeffrey D Hasday
BACKGROUND: As environmental and body temperatures vary, lung epithelial cells experience temperatures significantly different from normal core temperature. Our previous studies in human lung epithelium showed that: (i) heat shock accelerates wound healing and activates profibrotic gene expression through heat shock factor-1 (HSF1); (ii) HSF1 is activated at febrile temperatures (38-41 °C) and (iii) hypothermia (32 °C) activates and hyperthermia (39.5 °C) reduces expression of a subset of miRNAs that target protein kinase-Cα (PKCα) and enhance proliferation...
April 26, 2017: International Journal of Hyperthermia
https://www.readbyqxmd.com/read/28522797/protective-effects-of-hydrogen-rich-saline-against-lipopolysaccharide-induced-alveolar-epithelial-to-mesenchymal-transition-and-pulmonary-fibrosis
#6
Wen-Wen Dong, Yun-Qian Zhang, Xiao-Yan Zhu, Yan-Fei Mao, Xue-Jun Sun, Yu-Jian Liu, Lai Jiang
BACKGROUND Fibrotic change is one of the important reasons for the poor prognosis of patients with acute respiratory distress syndrome (ARDS). The present study investigated the effects of hydrogen-rich saline, a selective hydroxyl radical scavenger, on lipopolysaccharide (LPS)-induced pulmonary fibrosis. MATERIAL AND METHODS Male ICR mice were divided randomly into 5 groups: Control, LPS-treated plus vehicle treatment, and LPS-treated plus hydrogen-rich saline (2.5, 5, or 10 ml/kg) treatment. Twenty-eight days later, fibrosis was assessed by determination of collagen deposition, hydroxyproline, and type I collagen levels...
May 19, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28493530/m2-macrophages-induce-emt-through-the-tgf-%C3%AE-smad2-signaling-pathway
#7
Liangying Zhu, Xiao Fu, Xiang Chen, Xiaodong Han, Ping Dong
IPF is characterized by fibroblast accumulation, collagen deposition and ECM remodeling, with myofibroblasts believed to be the effector cell type. Myofibroblasts develop due to EMT of lung alveolar epithelial cells, which can be induced by TGF-β. M2 macrophages, a macrophage subpopulation, secrete large amounts of TGF-β. To clarify the relationship between IPF, EMT, TGF-β and M2 macrophages, a bleomycin-induced pulmonary fibrosis mouse model was used. Seventeen days after mice were treated with bleomycin, the successful establishment of a pulmonary fibrosis model was confirmed by HE stain and Masson's trichrome stain...
May 11, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28466866/posttreatment-with-protectin-dx-ameliorates-bleomycin-induced-pulmonary-fibrosis-and-lung-dysfunction-in-mice
#8
Hui Li, Yu Hao, Huawei Zhang, Weiyang Ying, Dan Li, Yahe Ge, Binyu Ying, Bihuan Cheng, Qingquan Lian, Shengwei Jin
Protectin DX (10S,17S-dihydroxydocosa-4Z,7Z,11E,13Z,15E,19Z-hexaenoic acid) (PDX), generated from Ω-3 fatty docosahexaenoic acids, is believed to exert anti-inflammatory and proresolution bioactions. To date, few studies have been performed regarding its effect on pulmonary fibrosis. Herein we show that PDX exerts a potential therapeutic effect which is distinct from its anti-inflammation and pro-resolution activity on mice with pulmonary fibrosis. In the present study, we showed that bleomycin (BLM) increased inflammatory infiltration, collagen deposition, and lung dysfunction on day7 after challenged in mice...
May 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28424456/paraquat-poisoning-induced-pulmonary-epithelial-mesenchymal-transition-through-notch1-pathway
#9
Tiegang Li, Xiangming Yang, Shiyu Xin, Yan Cao, Nana Wang
Progressive pulmonary fibrosis is the most characteristic feature of subacute PQ poisoning. Epithelial-to-mesenchymal transition (EMT) is reported to be involved in the pulmonary fibrosis after PQ exposure. Recent evidence suggested Notch signaling is required for EMT. In this study, we investigated whether Notch1 and TGF-β1/Smad3 signaling was involved in EMT caused by PQ. It is demonstrated that A549 cells underwent EMT after treated with PQ at dose of 300 μmol/L for 6 days, charactered by increasing expression of mesenchymal marker α-SMA and decreasing expression of epithelial marker E-cadherin...
April 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28408209/role-of-mir-34a-in-tgf-%C3%AE-1-and-drug-induced-epithelial-mesenchymal-transition-in-alveolar-type-ii-epithelial-cells
#10
Mikihisa Takano, Chinami Nekomoto, Masashi Kawami, Ryoko Yumoto
Epithelial-mesenchymal transition (EMT) of alveolar type II epithelial cells may play an important role in the pulmonary fibrosis induced by drugs such as bleomycin (BLM) and methotrexate (MTX). In this study, we examined the role of microRNAs (miRNAs) in drug-induced EMT using RLE/Abca3, a cell line having alveolar type II cell-like phenotype. Based on the screening using miRNA microarray analysis, it was found that the expression of some miRNAs, such as miR-34a, was increased by transforming growth factor (TGF)-β1 and BLM...
April 10, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28386365/calpain-1-regulates-tgf-%C3%AE-1-induced-epithelial-mesenchymal-transition-in-human-lung-epithelial-cells-via-pi3k-akt-signaling-pathway
#11
Wei-Jun Tan, Qiu-Yue Tan, Ting Wang, Min Lian, Li Zhang, Zhen-Shun Cheng
Cell proliferation, transformation, and epithelial-mesenchymal transition (EMT) are key processes involved in the development of idiopathic pulmonary fibrosis (IPF). This study investigated the regulatory factors and signaling pathways that mediate EMT in the human type II alveolar epithelial A549 cell line. A549 cells were cultured in RPMI-1640 medium and allocated to the following four groups: blank control group or treated with transforming growth factor-β1 (TGF-β1), TGF-β1 + PD 150606 (a calpain 1 inhibitor), or PD 150606...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28341659/chronic-microaspiration-of-bile-acids-induces-lung-fibrosis-through-multiple-mechanisms-in-rats
#12
Bi Chen, Wen Jie You, Xue Qing Liu, Shan Xue, Hui Qin, Han Dong Jiang
Gastroesophageal reflux (GER) and microaspiration of duodenogastric refluxate have been recognized as a risk factor for pulmonary fibrosis. Recent evidence suggests that bile acid microaspiration may contribute to the development of lung fibrosis. However, the molecular evidence is scarce and the underlying mechanisms remain to be elucidated. We have recently demonstrated that bile acids induce activation of alveolar epithelial cells (AECs) and lung fibroblasts in vitro In the present study, a rat model of bile acid microaspiration was established by weekly intratracheal instillation of three major bile acids including chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), and lithocholic acid (LCA)...
May 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28322466/the-role-of-mir-497-eif3a-axis-in-tgf%C3%AE-1-induced-epithelial-mesenchymal-transition-and-extracellular-matrix-in-rat-alveolar-epithelial-cells-and-pulmonary-fibroblasts
#13
Ren Guo, Yu Lv, Yang Ouyang, Siyu Liu, Dai Li
Multi-cause-induced interstitial lung disease, particularly pulmonary fibrosis, is a serious clinical concern. Fibroblasts have been suggested to have a major role, with it recently being revealed that some of these fibroblasts are derived from alveolar epithelial cells through epithelial-mesenchymal transition (EMT). Eukaryotic translation initiation factor 3 subunit A (EIF3A) is a protein that in humans is encoded by the EIF3A gene, and has been suggested to play roles in regulating translation of a subset of mRNAs and in regulating cell cycle progression and cell proliferation...
March 21, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28315789/involvement-of-epithelial-mesenchymal-transition-afforded-by-activation-of-lox-1-tgf-%C3%AE-1-klf6-signaling-pathway-in-diabetic-pulmonary-fibrosis
#14
Xiao-Zhou Zou, Zhi-Cheng Gong, Ting Liu, Fang He, Tian-Tian Zhu, Dai Li, Wei-Fang Zhang, Jun-Lin Jiang, Chang-Ping Hu
BACKGROUND AND OBJECTIVE: Diabetic pulmonary fibrosis is a severe disease that increases mortality risk of diabetes. However, the molecular mechanisms leading to pulmonary fibrosis in diabetes are poorly understood. This study investigated the roles of epithelial-mesenchymal transition (EMT) and the associated molecular mechanisms in streptozotocin (STZ)-induced rat pulmonary fibrosis. METHODS: The rat model of diabetic pulmonary fibrosis was established by intraperitoneal injection of a single dose of STZ (35 mg/kg)...
June 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28315692/role-of-epithelial-mesenchymal-transition-emt-and-fibroblast-function-in-cerium-oxide-nanoparticles-induced-lung-fibrosis
#15
Jane Ma, Bridget Bishoff, R R Mercer, Mark Barger, Diane Schwegler-Berry, Vincent Castranova
The emission of cerium oxide nanoparticles (CeO2) from diesel engines, using cerium compounds as a catalyst to lower the diesel exhaust particles, is a health concern. We have previously shown that CeO2 induced pulmonary inflammation and lung fibrosis. The objective of the present study was to investigate the modification of fibroblast function and the role of epithelial-mesenchymal transition (EMT) in CeO2-induced fibrosis. Male Sprague-Dawley rats were exposed to CeO2 (0.15 to 7mg/kg) by a single intratracheal instillation and sacrificed at various times post-exposure...
May 15, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28285699/pirfenidone-plays-a-biphasic-role-in-inhibition-of-epithelial-mesenchymal-transition-in-non-small-cell-lung-cancer
#16
Ayako Fujiwara, Yasushi Shintani, Soichiro Funaki, Tomohiro Kawamura, Toru Kimura, Masato Minami, Meinoshin Okumura
INTRODUCTION: Epithelial to mesenchymal transition (EMT) relates to both organ fibrosis and malignant behavior of cancer. Pirfenidone (PFD) is an anti-fibrotic agent for idiopathic pulmonary fibrosis and one of its functions may be to inhibit fibrotic EMT. This study aimed to investigate the possibility that PFD might exert an anti-tumor effect through inhibition of EMT in non-small cell lung cancer (NSCLC) cell lines in vitro and in vivo. METHODS: NSCLC cells (A549, NCI-H358) were used to evaluate PFD effects on TGF-β1 induced phenotypic changes...
April 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28274525/epithelial-and-endothelial-cell-plasticity-in-chronic-obstructive-pulmonary-disease-copd
#17
REVIEW
Sukhwinder Singh Sohal
Chronic Obstructive Pulmonary Disease (COPD) is mainly caused by smoking and presents with shortness of breath that is progressive and irreversible. It is a worldwide health problem and the fourth most common cause of chronic disability and mortality (even in developed countries). It is a complex disease involving both the airway and lung parenchyma. Small-airway fibrosis is the main contributor to physiological airway dysfunction in COPD. One potential mechanism contributing to small-airway fibrosis is epithelial mesenchymal transition (EMT)...
March 2017: Respiratory Investigation
https://www.readbyqxmd.com/read/28259823/evaluation-of-permeability-alteration-and-epithelial-mesenchymal-transition-induced-by-transforming-growth-factor-%C3%AE-1-in-a549-nci-h441-and-calu-3-cells-development-of-an-in-vitro-model-of-respiratory-epithelial-cells-in-idiopathic-pulmonary-fibrosis
#18
Kohei Togami, Kotaro Yamaguchi, Sumio Chono, Hitoshi Tada
INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease, which is accompanied by changes in lung structure. With regard to treatment, aerosolized drugs administered intrapulmonarily are rapidly distributed into the plasma and do not remain in the lungs due to damage to the alveolar epithelium that occurs from pulmonary fibrosis. In this study, we sought to develop an in vitro model of respiratory epithelial cells in IPF for the evaluation of the intrapulmonary distribution of aerosolized drugs...
March 1, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28239354/matrix-metalloproteinases-7-and-kidney-fibrosis
#19
REVIEW
Ben Ke, Chuqiao Fan, Liping Yang, Xiangdong Fang
Matrix metalloproteinase-7 (MMP-7) is a secreted zinc- and calcium-dependent endopeptidase that degrades a broad range of extracellular matrix substrates and additional substrates. MMP-7 playsa crucial role in a diverse array of cellular processes and appears to be a key regulator of fibrosis in several diseases, including pulmonary fibrosis, liver fibrosis, and cystic fibrosis. In particular, the relationship between MMP-7 and kidney fibrosis has attracted significant attention in recent years. Growing evidence indicates that MMP-7 plays an important role in the pathogenesis of kidney fibrosis...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28131417/mir-18a-5p-inhibits-sub-pleural-pulmonary-fibrosis-by-targeting-tgf-%C3%AE-receptor-ii
#20
Qian Zhang, Hong Ye, Fei Xiang, Lin-Jie Song, Li-Ling Zhou, Peng-Cheng Cai, Jian-Chu Zhang, Fan Yu, Huan-Zhong Shi, Yunchao Su, Jian-Bao Xin, Wan-Li Ma
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease that typically leads to respiratory failure and death within 3-5 years of diagnosis. Sub-pleural pulmonary fibrosis is a pathological hallmark of IPF. Bleomycin treatment of mice is a an established pulmonary fibrosis model. We recently showed that bleomycin-induced epithelial-mesenchymal transition (EMT) contributes to pleural mesothelial cell (PMC) migration and sub-pleural pulmonary fibrosis. MicroRNA (miRNA) expression has recently been implicated in the pathogenesis of IPF...
March 1, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
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