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EMT and pulmonary fibrosis

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https://www.readbyqxmd.com/read/29774214/the-expression-of-aqp1-is-modified-in-lung-of-patients-with-idiopathic-pulmonary-fibrosis-addressing-a-possible-new-target
#1
Ana Galán-Cobo, Elena Arellano-Orden, Rocío Sánchez Silva, José Luis López-Campos, César Gutiérrez Rivera, Lourdes Gómez Izquierdo, Nela Suárez-Luna, María Molina-Molina, José A Rodríguez Portal, Miriam Echevarría
Activation of the epithelial-mesenchymal transition process (EMT) by which alveolar cells in human lung tissue undergo differentiation giving rise to a mesenchymal phenotype (fibroblast/miofibroblasts) has been well recognized as a key element in the origin of idiopathic pulmonary fibrosis (IPF). Here we analyzed expression of AQP1 in lung biopsies of patients diagnosed with IPF, and compared it to biopsies derived from patients with diverse lung pneumonies, such as hypersensitivity pneumonitis, sarcoidosis or normal lungs...
2018: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/29740320/amifostine-analog-drde-30-attenuates-bleomycin-induced-pulmonary-fibrosis-in-mice
#2
Aastha Arora, Vikas Bhuria, Puja P Hazari, Uma Pathak, Sweta Mathur, Bal G Roy, Rajat Sandhir, Ravi Soni, Bilikere S Dwarakanath, Anant N Bhatt
Bleomycin (BLM) is an effective curative option in the management of several malignancies including pleural effusions; but pulmonary toxicity, comprising of pneumonitis and fibrosis, poses challenge in its use as a front-line chemotherapeutic. Although Amifostine has been found to protect lungs from the toxic effects of radiation and BLM, its application is limited due to associated toxicity and unfavorable route of administration. Therefore, there is a need for selective, potent, and safe anti-fibrotic drugs...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29705800/histone-deacetylases-promote-er-stress-induced-epithelial-mesenchymal-transition-in-human-lung-epithelial-cells
#3
Daishun Liu, Honglan Zhu, Ling Gong, Shenglan Pu, Yang Wu, Wei Zhang, Guichuan Huang
BACKGROUND/AIMS: Epithelial to mesenchymal transition (EMT) is a crucial process involved in pulmonary fibrosis. This study aimed to explore the role of histone deacetylases (HDACs) and endoplasmic reticulum (ER) stress in EMT in human lung epithelial cells. METHODS: Human lung adenocarcinoma A549 cells were treated with bleomycin and tunicamycin to induce EMT. The proliferation of A549 cells was detected by MTT assay. The expression of HDACs and EMT markers was detected by PCR and Western blot analysis...
April 25, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29704504/inhibition-of-mtor-ameliorates-bleomycin-induced-pulmonary-fibrosis-by-regulating-epithelial-mesenchymal-transition
#4
Qian Han, Lianjun Lin, Beilei Zhao, Nanping Wang, Xinmin Liu
Epithelial-mesenchymal transition (EMT) plays a pivotal role in idiopathic pulmonary fibrosis (IPF). In bleomycin-induced pulmonary fibrosis mice, we observed that inhibition of mTOR (mammalia target of rapamycin) attenuated IPF. Rapamycin suppressed the down-regulation of E-cadherin and up-regulation of fibronectin in bleomycin-induced pulmonary fibrosis mice. In addition, dual immunofluorescence staining for E-cadherin and fibronectin demonstrated that rapamycin pretreatment decreased the proportions of AECs undergoing EMT in bleomycin-induced pulmonary fibrosis, indicating that mTOR inhibition suppressed EMT in vivo...
May 2, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29683754/micrornas-in-idiopathic-pulmonary-fibrosis-new-research-progress-and-their-pathophysiological-implication
#5
Chenggui Miao, Youyi Xiong, Guoxue Zhang, Jun Chang
Many studies have shown that microRNAs (miRNAs) play important roles in the development of idiopathic pulmonary fibrosis (IPF). The purpose of this review is to systematically summarize the recent advance of miRNAs in the pathology of IPF, highlighting the new research progress and their pathophysiological implication. Recent studies have shown that miRNAs differentially expressed in blood and lung tissue from IPF patients are closely related to the occurrence of IPF disease, which may be IPF diagnostic markers and prognostic indicators...
April 23, 2018: Experimental Lung Research
https://www.readbyqxmd.com/read/29677166/in-vitro-identification-of-new-transcriptomic-and-mirnomic-profiles-associated-with-pulmonary-fibrosis-induced-by-high-doses-everolimus-looking-for-new-pathogenetic-markers-and-therapeutic-targets
#6
Simona Granata, Gloria Santoro, Valentina Masola, Paola Tomei, Fabio Sallustio, Paola Pontrelli, Matteo Accetturo, Nadia Antonucci, Pierluigi Carratù, Antonio Lupo, Gianluigi Zaza
The administration of Everolimus (EVE), a mTOR inhibitor used in transplantation and cancer, is often associated with adverse effects including pulmonary fibrosis. Although the underlying mechanism is not fully clarified, this condition could be in part caused by epithelial to mesenchymal transition (EMT) of airway cells. To improve our knowledge, primary bronchial epithelial cells (BE63/3) were treated with EVE (5 and 100 nM) for 24 h. EMT markers (α-SMA, vimentin, fibronectin) were measured by RT-PCR. Transepithelial resistance was measured by Millicell-ERS ohmmeter...
April 20, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29676583/reticulocalbin-3-deficiency-in-alveolar-epithelium-exacerbated-bleomycin-induced-pulmonary-fibrosis
#7
Jiawei Jin, Xiaoqian Shi, Yongchao Li, Qianyu Zhang, Yu Guo, Chaokun Li, Pingping Tan, Qiuhong Fang, Yingmin Ma, Runlin Z Ma
Reticulocalbin 3 (Rcn3) is an endoplasmic reticulum (ER) lumen protein localized to the secretory pathway. We have reported that Rcn3 plays critical role for alveolar epithelial cell type II (AECII) maturation during perinatal lung development, but its biological role in the adult lung is largely unknown. Herein, we found marked induction of Rcn3 expression in alveolar epithelium during bleomycin-induced pulmonary fibrosis, which is most obvious in AECIIs. To further examine Rcn3 in pulmonary injury-remodeling, we generated transgenic mice to selectively delete Rcn3 in AECIIs in adulthood...
April 20, 2018: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29666896/calpain-inhibition-attenuates-bleomycin-induced-pulmonary-fibrosis-via-switching-the-development-of-epithelial-mesenchymal-transition
#8
Yuan Liu, Bing Liu, Gu-Qin Zhang, Jing-Feng Zou, Meng-Lin Zou, Zhen-Shun Cheng
Calpains are intracellular calcium-dependent cysteine proteases, which cleave several substrates proteins, have been proven to play important roles in lung fibrosis. The aim of this study was to investigate the effects of calpain on bleomycin (BLM)-induced pulmonary fibrosis. A lung fibrosis mice model was established successfully by intraperitoneal injection of bleomycin. Calpeptin, a highly selective inhibitor of calpain activation, was administered three times weekly after bleomycin injection. Histological examination was used to assess the fibrosis...
April 18, 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/29623041/an-adaptogen-withaferin-a-ameliorates-in-vitro-and-in-vivo-pulmonary-fibrosis-by-modulating-the-interplay-of-fibrotic-matricelluar-proteins-and-cytokines
#9
Swarna Bale, Pooladanda Venkatesh, Manoj Sunkoju, Chandraiah Godugu
Pulmonary fibrosis (PF) is chronic lung disease with only two FDA approved clinically available drugs, with limited safety profile. Inadequate therapy motivated us to explore the effect of vimentin inhibitor Withaferin A, as an anti-fibrotic agent against TGF-β1-induced in vitro fibrotic events and Bleomycin induced in vivo fibrosis with an emphasis on epithelial to mesenchymal transition (EMT), extracellular matrix deposition (ECM), inflammation, and angiogenesis. In vitro EMT and fibrotic events were induced by TGF-β1 in alveolar epithelial cells and human fetal lung fibroblasts followed by treatment with Withaferin A (0...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29609658/sulforaphane-attenuates-pulmonary-fibrosis-by-inhibiting-the-epithelial-mesenchymal-transition
#10
Sun Young Kyung, Dae Young Kim, Jin Young Yoon, Eun Suk Son, Yu Jin Kim, Jeong Woong Park, Sung Hwan Jeong
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease with no effective treatment. The epithelial-mesenchymal transition (EMT) is a critical stage during the development of fibrosis. To assess the effect of sulforaphane (SFN) on the EMT and fibrosis using an in vitro transforming growth factor (TGF)-β1-induced model and an in vivo bleomycin (BLM)-induced model. METHODS: In vitro studies, cell viability, and cytotoxicity were measured using a Cell Counting Kit-8...
April 2, 2018: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29604596/submicron-emulsion-of-cinnamaldehyde-ameliorates-bleomycin-induced-idiopathic-pulmonary-fibrosis-via-inhibition-of-inflammation-oxidative-stress-and-epithelial-mesenchymal-transition
#11
Li Yan, Fan Song, Hua Li, Yao Li, Jie Li, Qiao-Yan He, Di Zhang, Fang Wang, Meng Zhang, Hang Zhao, Tian Feng, Ying-Yong Zhao, Si-Wang Wang
AIMS: Idiopathic pulmonary fibrosis (IPF) is the most frequent and severe form of idiopathic interstitial pneumonias. The pathogenesis is associated with inflammation and oxidative stress and epithelial-mesenchymal transition (EMT). Cinnamaldehyde exhibits antiinflammatory and antioxidant properties, but its effect on IPF is unknown. The present study is to investigate the anti-fibrotic effect and action mechanism of cinnamaldehyde on IPF. MATERIALS AND METHODS: IPF was induced by intratracheal bleomycin in mice...
March 28, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29581578/heparin-binding-epidermal-growth-factor-contributes-to-copd-disease-severity-by-modulating-airway-fibrosis-and-pulmonary-epithelial-mesenchymal-transition
#12
Tianwen Lai, Yanyu Li, Min Chen, Guihai Pan, Xiaoxia Wen, Zongjiong Mai, Yalian Yuan, Yingying Lv, Quanchao Lv, Ruilian Cen, Huajuan Yi, Mengling Wen, Dongming Li, Bin Wu, Dong Wu, Chao Cao
Although airway fibrosis and epithelial-mesenchymal transition (EMT) contribute to airway remodeling in chronic obstructive pulmonary disease (COPD), the mechanisms underlying their development have not been fully elucidated. In the present study, we aimed to assess heparin-binding epidermal growth factor (HB-EGF) expression in the airways of patients with COPD and to elucidate the possible role of HB-EGF in the pathology of COPD. Sputum and lung tissue HB-EGF expression was evaluated in control subjects and patients with COPD...
March 26, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29540674/circhectd1-promotes-the-silica-induced-pulmonary-endothelial-mesenchymal-transition-via-hectd1
#13
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
https://www.readbyqxmd.com/read/29532266/ibrutinib-exacerbates-bleomycin-induced-pulmonary-fibrosis-via-promoting-inflammation
#14
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
https://www.readbyqxmd.com/read/29531814/2-aminopurine-suppresses-the-tgf-%C3%AE-1-induced-epithelial-mesenchymal-transition-and-attenuates-bleomycin-induced-pulmonary-fibrosis
#15
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
https://www.readbyqxmd.com/read/29529050/transmembrane-protease-serine-4-tmprss4-is-upregulated-in-ipf-lungs-and-increases-the-fibrotic-response-in-bleomycin-induced-lung-injury
#16
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
https://www.readbyqxmd.com/read/29524411/leptin-promotes-pulmonary-fibrosis-development-by-inhibiting-autophagy-via-pi3k-akt-mtor-pathway
#17
Xianhua Gui, Hongwei Chen, Hourong Cai, Lingyun Sun, Luo Gu
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...
April 6, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29467842/hypoxia-inducible-factor-1%C3%AE-regulates-epithelial-to-mesenchymal-transition-in-paraquat-induced-pulmonary-fibrosis-by-activating-lysyl-oxidase
#18
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
https://www.readbyqxmd.com/read/29448106/folic-acid-prevents-methotrexate-induced-epithelial-mesenchymal-transition-via-suppression-of-secreted-factors-from-the-human-alveolar-epithelial-cell-line-a549
#19
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 26, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29417309/il-33-can-promote-the-process-of-pulmonary-fibrosis-by-inducing-the-imbalance-between-mmp-9-and-timp-1
#20
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
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