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EMT and pulmonary fibrosis

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https://www.readbyqxmd.com/read/27911568/nf%C3%AE%C2%BAb-mediates-mesenchymal-transition-remodeling-and-pulmonary-fibrosis-in-response-to-chronic-inflammation-by-viral-rna-patterns
#1
Bing Tian, Igor Patrikeev, Lorenzo Ochoa, Gracie Vargas, KarryAnne K Belanger, Julia Litvinov, Istvan Boldogh, Bill T Ameredes, Massoud Motamedi, Allan R Brasier
Airway remodeling is resultant of a complex multi-cellular response associated with a progressive decline of pulmonary function in patients with chronic airway disease. Here, repeated infections with respiratory viruses are linked with airway remodeling through largely unknown mechanisms. Although acute activation of the Toll like receptor (TLR)3 pathway by extracellular poly(I:C) induces innate signaling through the NFkB transcription factor in human small airway epithelial cells (hSAECs), prolonged (repetitive or tonic) poly(I:C) stimulation produces chronic stress fiber formation, mesenchymal transition and activation of a fibrotic program...
December 2, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27909724/hsp27-regulates-tgf-%C3%AE-mediated-lung-fibroblast-differentiation-through-the-smad3-and-erk-pathways
#2
Gang Wang, Hao Jiao, Jun-Nian Zheng, Xia Sun
Idiopathic pulmonary fibrosis (IPF) is a chronic lethal interstitial lung disease with unknown etiology. Recent studies have indicated that heat-shock protein 27 (HSP27) contributes to the pathogenesis of IPF through the regulation of epithelial-mesenchymal transition (EMT). However, the expression and role of HSP27 in fibroblasts during pulmonary fibrogenesis has not been investigated to date, at least to the best of our knowledge. In this study, we examined the expression of HSP27 in fibrotic lung tissue and fibroblasts from bleomycin (BLM)-challenged mice and human lung fibroblasts treated with transforming growth factor-β (TGF-β)...
November 28, 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27895584/induced-pluripotent-stem-cells-inhibit-bleomycin-induced-pulmonary-fibrosis-in-mice-through-suppressing-tgf-%C3%AE-1-smad-mediated-epithelial-to-mesenchymal-transition
#3
Yan Zhou, Zhong He, Yuan Gao, Rui Zheng, Xiaoye Zhang, Li Zhao, Mingqi Tan
Pulmonary fibrosis is a progressive and irreversible fibrotic lung disorder with high mortality and few treatment options. Recently, induced pluripotent stem (iPS) cells have been considered as an ideal resource for stem cell-based therapy. Although, an earlier study demonstrated the therapeutic effect of iPS cells on pulmonary fibrosis, the exact mechanisms remain obscure. The present study investigated the effects of iPS cells on inflammatory responses, transforming growth factor (TGF)-β1 signaling pathway, and epithelial to mesenchymal transition (EMT) during bleomycin (BLM)-induced lung fibrosis...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27878256/melatonin-attenuates-tgf%C3%AE-1-induced-epithelial-mesenchymal-transition-in-lung-alveolar-epithelial-cells
#4
Na Yu, Yi-Tian Sun, Xin-Ming Su, Miao He, Bing Dai, Jian Kang
Idiopathic pulmonary fibrosis (IPF) is the most common interstitial lung disease. However, the pathogenesis remains to be fully elucidated. Melatonin is secreted by the pineal gland, it has a strong antioxidant effect, and exerts an anti-fibrosis effect. Whether melatonin attenuates pulm -onary fibrosis by inhibiting epithelial‑mesenchymal transition (EMT) requires further research. The present study aimed to investigate whether melatonin prevents transforming growth factor‑β1 (TGF‑β1)‑induced EMT and underlying signaling pathways using reverse transcription‑quantitative polymerase chain reaction, western blot analysis and immunofluorescence...
November 16, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27793799/brd4-mediates-nf%C3%AE%C2%BAb-dependent-epithelial-mesenchymal-transition-and-pulmonary-fibrosis-via-transcriptional-elongation
#5
Bing Tian, Yingxin Zhao, Hong Sun, Yueqing Zhang, Jun Yang, Allan R Brasier
Chronic epithelial injury triggers a TGFβ-mediated cellular transition from normal epithelium into a mesenchymal-like state that produces subepithelial fibrosis and airway remodeling. Here we examined how TGFβ induces the mesenchymal cell state, and determined its mechanism. We observe that TGFβ stimulation activates an inflammatory gene program controlled by the NFκB/RelA signaling pathway. In the mesenchymal state, NFκB-dependent immediate-early genes accumulate euchromatin marks and processive RNA polymerase...
October 28, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27790277/increased-cellular-nad-level-through-nqo1-enzymatic-action-has-protective-effects-on-bleomycin-induced-lung-fibrosis-in-mice
#6
Gi-Su Oh, Su-Bin Lee, Anjani Karna, Hyung-Jin Kim, AiHua Shen, Arpana Pandit, SeungHoon Lee, Sei-Hoon Yang, Hong-Seob So
BACKGROUND: Idiopathic pulmonary fibrosis is a common interstitial lung disease; it is a chronic, progressive, and fatal lung disease of unknown etiology. Over the last two decades, knowledge about the underlying mechanisms of pulmonary fibrosis has improved markedly and facilitated the identification of potential targets for novel therapies. However, despite the large number of antifibrotic drugs being described in experimental pre-clinical studies, the translation of these findings into clinical practices has not been accomplished yet...
October 2016: Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/27774992/emodin-ameliorates-bleomycin-induced-pulmonary-fibrosis-in-rats-by-suppressing-epithelial-mesenchymal-transition-and-fibroblast-activation
#7
Ruijuan Guan, Xia Wang, Xiaomei Zhao, Nana Song, Jimin Zhu, Jijiang Wang, Jin Wang, Chunmei Xia, Yonghua Chen, Danian Zhu, Linlin Shen
Aberrant activation of TGF-β1 is frequently encountered and promotes epithelial-mesenchymal transition (EMT) and fibroblast activation in pulmonary fibrosis. The present study investigated whether emodin mediates its effect via suppressing TGF-β1-induced EMT and fibroblast activation in bleomycin (BLM)-induced pulmonary fibrosis in rats. Here, we found that emodin induced apoptosis and inhibited cellular proliferation, migration and differentiation in TGF-β1-stimulated human embryonic lung fibroblasts (HELFs)...
October 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27604426/methotrexate-induced-epithelial-mesenchymal-transition-in-the-alveolar-epithelial-cell-line-a549
#8
Masashi Kawami, Rika Harabayashi, Mioka Miyamoto, Risako Harada, Ryoko Yumoto, Mikihisa Takano
PURPOSE: Methotrexate (MTX) therapy of certain cancers and rheumatoid arthritis often induces serious interstitial lung complications including pulmonary fibrosis. In this study, we investigated the epithelial-mesenchymal transition (EMT) induced by MTX and by transforming growth factor (TGF)-β1 in the human alveolar epithelial cell line A549 in order to develop new strategies for the prevention of EMT. METHODS: First, we examined the effect of TGF-β1 and MTX on cell morphology and the expression of EMT-related mRNAs in A549 cells...
September 7, 2016: Lung
https://www.readbyqxmd.com/read/27513632/mir%C3%A2-221-targets-hmga2-to-inhibit-bleomycin%C3%A2-induced-pulmonary-fibrosis-by-regulating-tgf%C3%A2-%C3%AE-1-smad3-induced-emt
#9
Yi-Chun Wang, Jing-Shi Liu, Hao-Ke Tang, Jing Nie, Ji-Xian Zhu, Ling-Ling Wen, Qu-Lian Guo
MicroRNA (miR)-221 plays an essential role in the epithelial-mesenchymal transition (EMT). High mobility group AT-hook 2 (HMGA2), is a key regulator of EMT. However, the role of miR‑221 in pulmonary fibrosis, and the association between miR‑221 and HMGA2 remain largely unknown. For this purpose, we examined the expression of miR‑221 and HMGA2 in human idiopathic pulmonary fibrosis (IPF) tissues and pulmonary cells, namely the adenocarcinoma A549 and human bronchial epithelium (HBE) cell lines, and found that the expression of miR‑221 was inhibited in both tissues and cells whereas high mRNA and protein expression of HMGA2 was observed...
October 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27508042/mir-338-targeting-smoothened-to-inhibit-pulmonary-fibrosis-by-epithelial-mesenchymal-transition
#10
Yi Zhuang, Jinghong Dai, Yongsheng Wang, Huan Zhang, Xinxiu Li, Chunli Wang, Mengshu Cao, Yin Liu, Jingjing Ding, Hourong Cai, Deping Zhang, Yaping Wang
Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease involving pulmonary injury associated with tissue repair, dysfunction and fibrosis. Recent studies indicate that some microRNAs (miRNAs) may play critical roles in the pathogenesis of pulmonary fibrosis. In this study, we aim to investigate whether miR-338* (miR-338-5p), which has been found to be associated with tumor progression, is associated with pathological process of pulmonary fibrosis. Balb/c mice were treated with bleomycin (BLM) to establish IPF models...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27498952/little-evidence-for-epithelial-mesenchymal-transition-in-a-murine-model-of-airway-fibrosis-induced-by-repeated-naphthalene-exposure
#11
Osamu Watanabe, Takao Tsuji, Ryota Kikuchi, Masayuki Itoh, Hiroyuki Nakamura, Kazutetsu Aoshiba
Recent evidence suggests that epithelial-mesenchymal transition (EMT) is involved in the pathogenesis of airway obstructive diseases, such as chronic obstructive pulmonary disease, asthma and bronchiolitis obliterans syndrome after lung transplantation. However, whether EMT occurs in an experimental model of airway fibrosis is not well known. We explored evidence of EMT in a murine model of airway fibrosis induced by repeated exposure to naphthalene. Mice were administered intraperitoneal injections of naphthalene or corn oil vehicle once weekly for 14 consecutive weeks...
October 2016: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
https://www.readbyqxmd.com/read/27495007/d-4f-an-apolipoprotein-a-i-mimetic-inhibits-tgf-%C3%AE-1-induced-epithelial-mesenchymal-transition-in-human-alveolar-epithelial-cell
#12
Jia You, Jintao Wang, Linshen Xie, Chengwen Zhu, Jingyuan Xiong
Emerging evidences support that transforming growth factor β1 (TGF-β1) induced epithelial-mesenchymal transition (EMT) participates in the pathogenesis of pulmonary fibrosis and asthmatic airway remodeling. Recent studies demonstrated that apolipoprotein A-I (Apo A-I) is the only known substance that can resolve established pulmonary fibrotic nodules, and Apo A-I mimetic D-4F (a synthetic polypeptide consisting of 18 amino acids) plays an inhibitory role in murine asthmatic model. However, cellular mechanisms for such therapeutic effects of Apo A-I and D-4F remain to be elucidated...
October 2016: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
https://www.readbyqxmd.com/read/27471572/bleomycin-blm-induces-epithelial-to-mesenchymal-transition-in-cultured-a549-cells-via-the-tgf-%C3%AE-smad-signaling-pathway
#13
Kui-Jun Chen, Qing Li, Cang-Mei Wen, Zhao-Xia Duan, Jie Yuan Zhang, Chuan Xu, Jian-Min Wang
The epithelial-to-mesenchymal transition (EMT) is a crucial cellular event in wound healing, tissue repair, and cancer progression in adult tissues, with the interactions with numerous signals. In this study, we aimed to determine whether bleomycin (BLM), an agent that causes pulmonary fibrosis, induces the EMT of the alveolar epithelial cell line A549 and investigated the possible mechanisms. We examined the EMT involved changes in cell morphology, isoform switching of the fibroblast growth factor receptor 2 (FGFR2) by alternative splicing, and expression of the phenotypic markers including E-cadherin, vimentin, and α-SMA using RT-PCR, Western blotting, and immunofluorescence assays...
2016: Journal of Cancer
https://www.readbyqxmd.com/read/27461979/integrative-proteomic-analysis-reveals-reprograming-tumor-necrosis-factor-signaling-in-epithelial-mesenchymal-transition
#14
Yingxin Zhao, Bing Tian, Rovshan G Sadygov, Yueqing Zhang, Allan R Brasier
UNLABELLED: The airway epithelium is a semi-impermeable barrier whose disruption by growth factor reprogramming is associated with chronic airway diseases of humans. Transforming growth factor beta (TGFβ)-induced epithelial mesenchymal transition (EMT) plays important roles in airway remodeling characteristic of idiopathic lung fibrosis, asthma and chronic obstructive pulmonary disease (COPD). Inflammation of the airways leads to airway injury and tumor necrosis factor alpha (TNFα) plays an important pro-inflammatory role...
October 4, 2016: Journal of Proteomics
https://www.readbyqxmd.com/read/27439438/sunitinib-a-small-molecule-kinase-inhibitor-attenuates-bleomycin-induced-pulmonary-fibrosis-in-mice
#15
Xiang Huang, Weicheng Wang, Huaqin Yuan, Jing Sun, Lele Li, Xingxin Wu, Jinhua Luo, Yanhong Gu
Idiopathic pulmonary fibrosis (IPF) is a chronic and ultimately fatal disease, characterized by excessive accumulation of fibroblasts, extensive deposition of extracellular matrix, and destruction of alveolar architecture. IPF is associated with an epithelial-dependent fibroblast-activated process, termed the epithelial-to-mesenchymal transition (EMT). However, there is still a lack of strategies to target EMT for the treatment of IPF. Sunitinib, a small-molecule multi-targeted tyrosine kinase inhibitor, targets multiple kinases that may play an important role in developing pulmonary fibrosis...
2016: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27433174/apolipoprotein-a1-inhibits-tgf-%C3%AE-1-induced-epithelial-to-mesenchymal-transition-of-alveolar-epithelial-cells
#16
Ae Rin Baek, Ji Min Lee, Hyun Jung Seo, Jong Sook Park, June Hyuk Lee, Sung Woo Park, An Soo Jang, Do Jin Kim, Eun Suk Koh, Soo Taek Uh, Yong Hoon Kim, Choon Sik Park
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease characterized by the accumulation of excessive fibroblasts and myofibroblasts in the extracellular matrix. The transforming growth factor β1 (TGF-β1)-induced epithelial-to-mesenchymal transition (EMT) is thought to be a possible source of fibroblasts/myofibroblasts in IPF lungs. We have previously reported that apolipoprotein A1 (ApoA1) has anti-fibrotic activity in experimental lung fibrosis. In this study, we determine whether ApoA1 modulates TGF-β1-induced EMT in experimental lung fibrosis and clarify its mechanism of action...
July 2016: Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/27432893/the-marine-derived-oligosaccharide-sulfate-ms80-a-novel-transforming-growth-factor-%C3%AE-1-inhibitor-reverses-epithelial-mesenchymal-transition-induced-by-transforming-growth-factor-%C3%AE-1-and-suppresses-tumor-metastasis
#17
Ji Zhou, Wenjie You, Guangqiang Sun, Yixuan Li, Bi Chen, Jing Ai, Handong Jiang
Metastasis accounts for the majority of cancer-related deaths. Transforming growth factor β (TGF-β) is believed to promote late-stage cancer progression and metastasis by inducing epithelial-mesenchymal transition (EMT). We previously reported that MS80, a novel oligosaccharide sulfate, inhibits TGF-β1-induced pulmonary fibrosis by binding TGF-β1. In our study MS80 effectively inhibited TGF-β/Smad signaling in lung cancer cells, breast cancer cells, and model cell lines. In addition, MS80 inhibited TGF-β1-induced EMT, motility, and invasion in vitro...
October 2016: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27420297/regulatory-mechanisms-of-tgf-%C3%AE-1-induced-fibrogenesis-of-human-alveolar-epithelial-cells
#18
Lin Shi, Nian Dong, Xiaocong Fang, Xiangdong Wang
Pulmonary fibrosis is characterized by an extensive activation of fibrogenic cells and deposition of extracellular matrix (ECM). Transforming growth factor (TGF)-β1 plays a pivotal role in the pathogenesis of pulmonary fibrosis, probably through the epithelial- to-mesenchymal transition (EMT) and ECM production. The present study investigates potential mechanism by which TGF-β1 induces EMT and ECM production in the fibrogenesis of human lung epithelial cells during pulmonary fibrosis. The expression of EMT phenotype and other proteins relevant to fibrogenesis were measured and the cell bio-behaviours were assessed using Cell-IQ Alive Image Monitoring System...
July 15, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27373364/-regulation-effect-of-%C3%AE-catenin-pathway-on-tgf-%C3%AE-1-induced-pulmonary-pro-fibrosis
#19
X R Tian, X L Tian, H F Wang, Q Chang, R J Huo, D L Ying, G P Zheng
OBJECTIVE: To investigate the regulation effect of β-catenin pathway on transforming growth factor beta1 (TGF-β1) induced pulmonary pro-fibrosis. METHODS: The rat alveolar typeⅡ cells (RLE-6TN) were divided into four groups: A1.control group; B1.TGF-β1 group was treated with 5 μg/L TGF-β1; C1.pcDNA+ TGF-β1 group was transiently transfected with eukaryotic expression vector pcDNA3.0 (pcDNA) and followed by TGF-β1 treatment (5 μg/L); D1.F-(β-TrCP)-Ecad+ TGF-β1 group was transiently transfected with β-catenin protein knockout vector [F-(β-TrCP)-Ecad] and followed by TGF-β1 treatment (5 μg/L)...
June 28, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/27340759/development-of-an-in-vitro-assay-to-evaluate-contractile-function-of-mesenchymal-cells-that-underwent-epithelial-mesenchymal-transition
#20
Yu Mikami, Hirotaka Matsuzaki, Hideyuki Takeshima, Kosuke Makita, Yasuhiro Yamauchi, Takahide Nagase
Fibrosis is often involved in the pathogenesis of various chronic progressive diseases such as interstitial pulmonary disease. Pathological hallmark is the formation of fibroblastic foci, which is associated with the disease severity. Mesenchymal cells consisting of the fibroblastic foci are proposed to be derived from several cell sources, including originally resident intrapulmonary fibroblasts and circulating fibrocytes from bone marrow. Recently, mesenchymal cells that underwent epithelial-mesenchymal transition (EMT) have been also supposed to contribute to the pathogenesis of fibrosis...
2016: Journal of Visualized Experiments: JoVE
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