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Epithelial to mesenchymal transition and fibrosis

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https://www.readbyqxmd.com/read/29790537/physical-defects-in-basement-membrane-mimicking-collagen-iv-matrices-trigger-cellular-emt-and-invasion
#1
Christopher Walter, Joshua T Davis, Jairaj Mathur, Amit Pathak
In fibrosis and cancer, degradation of basement membrane (BM) and cell invasion are considered as key outcomes of a cellular transformation called epithelial-mesenchymal transition (EMT). Here, we pose a converse question - can preexisting physical defects in the BM matrix cause EMT in normal epithelial cells? On a BM-mimicking matrix of collagen-IV-coated polyacrylamide (PA) gel, we have discovered a reverse phenomenon in which preexisting defects trigger EMT in normal epithelial cells. Through spatiotemporal measurements and simulations in silico, we demonstrate that the EMT precedes cellular mechanoactivation on defective matrices, but they occur concurrently on stiff matrices...
May 23, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/29789993/the-role-of-the-epithelial-to-mesenchymal-transition-emt-in-diseases-of-the-salivary-glands
#2
REVIEW
Margherita Sisto, Sabrina Lisi, Domenico Ribatti
The link between inflammatory microenvironment and cancer emerged in the last years as a decisive factor in the induction of the pathological epithelial-mesenchymal transition (EMT). The EMT induces changes of cell states converting the epithelial cells to mesenchymal cells when this program is fully executed and EMT has emerged as a central driver of tumor malignancy. Cellular pathways activated by chronic inflammation brought about by chronic infections, by immune-mediated diseases, or by dysregulated wound healing at sites of repetitive tissue injury, constitute risk factors or initial cell transformation and for cancer progression...
May 23, 2018: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/29789683/bmp-2-restoration-aids-in-recovery-from-liver-fibrosis-by-attenuating-tgf-%C3%AE-1-signaling
#3
Yueh-Hua Chung, Ying-Hsien Huang, Tien-Huei Chu, Chun-Lin Chen, Pey-Ru Lin, Shih-Chung Huang, Deng-Chyang Wu, Chao-Cheng Huang, Tsung-Hui Hu, Ying-Hsien Kao, Ming-Hong Tai
Transforming growth factor-β (TGF-β) plays a central role in hepatic fibrogenesis. This study investigated the function and mechanism of bone morphogenetic protein-2 (BMP-2) in regulation of hepatic fibrogenesis. BMP-2 expression in fibrotic liver was measured in human tissue microarray and mouse models of liver fibrosis induced by bile duct ligation surgery or carbon tetrachloride administration. Adenovirus-mediated BMP-2 gene delivery was used to test the prophylactic effect on liver fibrosis. Primary hepatic stellate cells (HSC), HSC-T6 and clone-9 cell lines were used to study the interplay between BMP-2 and TGF-β1...
May 22, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29789348/gestational-low-protein-intake-enhances-whole-kidney-mir-192-and-mir-200-family-expression-and-epithelial-to-mesenchymal-transition-in-rat-adult-male-offspring
#4
Letícia B Sene, Victor Hugo Gonçalves Rizzi, José A R Gontijo, Patricia A Boer
Studies have shown that adult offspring of mothers fed a protein-restricted diet during pregnancy present a pronounced reduction of nephron number associated with decreased fractional urinary sodium excretion and arterial hypertension. Additionally, recent advances in our understanding of the molecular pathways that govern the association of gestational nutritional restriction, intrauterine growth retardation and inflammation with impaired nephrogenesis, nephron underdosing and kidney fibrosis point to the epithelial to mesenchymal transition (EMT) as a common factor...
May 22, 2018: Journal of Experimental Biology
https://www.readbyqxmd.com/read/29775417/targeting-histone-methyltransferase-enhancer-of-zeste-homolog-2-inhibits-renal-epithelial-mesenchymal-transition-and-attenuates-renal-fibrosis
#5
Xiaoxu Zhou, Chongxiang Xiong, Evelyn Tolbert, Ting C Zhao, George Bayliss, Shougang Zhuang
Enhancer of zeste homolog-2 (EZH2) is a methyltransferase that induces histone H3 lysine 27 trimethylation (H3K27me3) and functions as an oncogenic factor in many cancer types. Its role in renal epithelial-mesenchymal transition (EMT) remains unknown. In this study, we found that EZH2 and H3K27me3 were highly expressed in mouse kidney with unilateral ureteral obstruction and cultured mouse kidney proximal tubular (TKPT) cells undergoing EMT. Inhibition of EZH2 with 3-deazaneplanocin A (3-DZNeP) attenuated renal fibrosis, which was associated with preserving E-cadherin expression and inhibiting Vimentin up-regulation in the obstructed kidney...
May 18, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29774544/functional-molecules-in-mesothelial-to-mesenchymal-transition-revealed-by-transcriptome-analyses
#6
Sara Namvar, Adrian S Woolf, Leo A H Zeef, Thomas Wilm, Bettina Wilm, Sarah E Herrick
Peritoneal fibrosis is a common complication of abdominal and pelvic surgery, and can also be triggered by peritoneal dialysis, resulting in treatment failure. In these settings, fibrosis is driven by activated myofibroblasts that are considered to be partly derived by mesothelial-to-mesenchymal transition (MMT). We hypothesised that if the molecular signature of MMT could be better defined, these insights could be exploited to block this pathological cellular transition. Rat peritoneal mesothelial cells were purified, using an antibody to HBME1, a protein present on mesothelial cell microvilli, and streptavidin nanobead technology...
May 17, 2018: Journal of Pathology
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
#7
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/29768059/pentabromopseudilin-a-myosin-v-inhibitor-suppresses-tgf-%C3%AE-activity-by-recruiting-the-type-ii-tgf-%C3%AE-receptor-to-lysosomal-degradation
#8
Wang Shih-Wei, Chung Chih-Ling, Yu-Chen Kao, René Martin, Hans-Joachim Knölker, Meng-Shin Shiao, Chun-Lin Chen
Pentabromopseudilin (PBrP) is a marine antibiotic isolated from the marine bacteria Pseudomonas bromoutilis and Alteromonas luteoviolaceus. PBrP exhibits antimicrobial, anti-tumour, and phytotoxic activities. In mammalian cells, PBrP is known to act as a reversible and allosteric inhibitor of myosin Va (MyoVa). In this study, we report that PBrP is a potent inhibitor of transforming growth factor-β (TGF-β) activity. PBrP inhibits TGF-β-stimulated Smad2/3 phosphorylation, plasminogen activator inhibitor-1 (PAI-1) protein production and blocks TGF-β-induced epithelial-mesenchymal transition in epithelial cells...
December 2018: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/29761840/ginsenoside-rg1-ameliorates-liver-fibrosis-via-suppressing-epithelial-to-mesenchymal-transition-and-reactive-oxygen-species-production-in-vitro-and-in-vivo
#9
Xiaoyu Wei, Yatang Chen, Wenxiang Huang
Liver fibrosis remains a major cause of morbidity and mortality with a complicated etiology and notorious complications, but there is a lack of efficacious therapeutics. Epithelial to mesenchymal transition (EMT) has a central role in the course of liver fibrosis, and thus, prevention of the development of EMT may control and even reverse liver fibrosis. This study aimed to examine the beneficial effect of ginsenoside Rg1, a phrenological active component isolated from Ginseng, and interrogate the mechanism in vitro and in vivo, with a focus on transforming growth factor-β (TGF-β)/Smad and Nrf2-mediated signaling pathways...
May 15, 2018: BioFactors
https://www.readbyqxmd.com/read/29759484/runt-related-transcription-factor-1-runx1-promotes-tgf-%C3%AE-induced-renal-tubular-epithelial-to-mesenchymal-transition-emt-and-renal-fibrosis-through-the-pi3k-subunit-p110%C3%AE
#10
Tong Zhou, Maocai Luo, Wei Cai, Siyuan Zhou, Danying Feng, Chundi Xu, Hongyan Wang
Renal fibrosis is widely considered a common mechanism leading to end-stage renal failure. Epithelial-to-mesenchymal transition (EMT) plays important roles in the pathogenesis of renal fibrosis. Runt-related transcription factor 1(RUNX1) plays a vital role in hematopoiesis via Endothelial-to-Hematopoietic Transition (EHT), a process that is conceptually similar to EMT, but its role in EMT and renal fibrosis is unclear. Here, we demonstrate that RUNX1 is overexpressed in the processes of TGF-β-induced partial EMT and renal fibrosis and that the expression level of RUNX1 is SMAD3-dependent...
May 11, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29746703/s100a8-a9-promotes-parenchymal-damage-and-renal-fibrosis-in-obstructive-nephropathy
#11
Alessandra Tammaro, Sandrine Florquin, Mascha Brok, Nike Claessen, Loes M Butter, Gwendoline J D Teske, Onno J de Boer, Thomas Vogl, Jaklien C Leemans, Mark C Dessing
Despite advances in our understanding of the mechanisms underlying progression of chronic kidney disease and the development of fibrosis, only limited efficacious therapies exist. The calcium binding protein S100A8/A9, is a damage-associated molecular pattern which can activate TLR4 or RAGE. Activation of these receptors is involved in the progression of renal fibrosis, however the role of S100A8/A9 herein remains unknown. Therefore, we analyzed S100A8/A9 expression in patients and mice with obstructive nephropathy and subjected wild-type and S100A9 KO mice lacking the heterodimer S100A8/A9 to Unilateral Ureteral Obstruction (UUO)...
May 10, 2018: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29740320/amifostine-analog-drde-30-attenuates-bleomycin-induced-pulmonary-fibrosis-in-mice
#12
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/29731246/gdf11-induces-kidney-fibrosis-renal-cell-epithelial-to-mesenchymal-transition-and-kidney-dysfunction-and-failure
#13
Marianne Pons, Leonidas G Koniaris, Sharon M Moe, Juan C Gutierrez, Aurora Esquela-Kerscher, Teresa A Zimmers
BACKGROUND: GDF11 modulates embryonic patterning and kidney organogenesis. Herein, we sought to define GDF11 function in the adult kidney and in renal diseases. METHODS: In vitro renal cell lines, genetic, and murine in vivo renal injury models were examined. RESULTS: Among tissues tested, Gdf11 was highest in normal adult mouse kidney. Expression was increased acutely after 5/6 nephrectomy, ischemia-reperfusion injury, kanamycin toxicity, or unilateral ureteric obstruction...
May 3, 2018: Surgery
https://www.readbyqxmd.com/read/29723851/transplantation-of-telocytes-attenuates-unilateral-ureter-obstruction-induced-renal-fibrosis-in-rats
#14
Long Zheng, Long Li, Guisheng Qi, Mushuang Hu, Chao Hu, Shuo Wang, Jiawei Li, Mingnan Zhang, Weitao Zhang, Yigang Zeng, Yi Zhang, Liping Li, Xuanchuan Wang, Miao Lin, Tongyu Zhu, Ruiming Rong
BACKGROUND/AIMS: Previous studies imply that telocytes may have a protective effect on fibrosis in various organs, including the liver, colon, and heart. The effect of telocytes on renal fibrosis remains unknown. Herein, this study was designed to investigate the effect of telocytes on renal fibrosis and the potential mechanisms involved. METHODS: In a unilateral ureteral obstruction (UUO)-induced renal fibrosis model, telocytes were injected via the tail vein every other day for 10 days...
April 28, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29719094/protective-effect-of-retinoic-acid-receptor-%C3%AE-on-hypoxia-induced-epithelial-to-mesenchymal-transition-of-renal-tubular-epithelial-cells-associated-with-tgf-%C3%AE-mmp-9-pathway
#15
Ling Gong, Ling Jiang, Yuanhan Qin, Xingbo Jiang, Kunling Song, Xueyun Yu
Retinoic acid receptor α (RARα), a member of family of the nuclear retinoic acid receptors (RARs), plays an essential role in various chronic kidney diseases (CKD). Renal tubular epithelial to mesenchymal transition (EMT) is a common mechanism of progression of renal interstitial fibrosis (RIF). Hypoxia has been extensively considered as one of major inducers of renal tubular EMT. However, the effects of RARα on hypoxia-induced EMT have not yet been described so far. The aim of the present study was to explore the roles and potential mechanisms of RARα in hypoxia-induced EMT of renal tubular epithelial cells (RTECs)...
May 2, 2018: Cell Biology International
https://www.readbyqxmd.com/read/29719047/echinococcus-granulosus-cyst-fluid-enhances-epithelial-mesenchymal-transition
#16
Ahmed A Mohammed, J Allen, M T Rogan
AIMS: Cystic Echinococcosis is characterised by fluid filled hydatid cysts in the liver and lungs. The cysts are surrounded by a host fibrous layer (the pericyst) which acts to isolate the parasite from surrounding tissues. Previous studies in liver cysts have indicated that the parasite may be stimulating fibrosis. The aim of this study was to investigate whether Hydatid Cyst Fluid (HCF) could influence the potential for fibrosis to occur in lung tissue by stimulating epithelial to mesenchymal transition (EMT) in a human lung epithelial cell line...
May 2, 2018: Parasite Immunology
https://www.readbyqxmd.com/read/29718762/in-wound-repair-vimentin-mediates-the-transition-of-mesenchymal-leader-cells-to-a-myofibroblast-phenotype
#17
J L Walker, B M Bleaken, A R Romisher, A A Alnwibit, A S Menko
Following injury, mesenchymal repair cells are activated to function as leader cells that modulate wound healing. These cells have the potential to differentiate to myofibroblasts, resulting in fibrosis and scarring. The signals underlying these differing pathways are complex and incompletely understood. The ex vivo mock cataract surgery cultures are an attractive model with which to address this question. With this model we study, concurrently, the mechanisms that control mesenchymal leader cell function in injury repair within their native microenvironment, and the signals that induce this same cell population to acquire a myofibroblast phenotype when these cells encounter the environment of the adjacent tissue culture platform...
May 2, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29705800/histone-deacetylases-promote-er-stress-induced-epithelial-mesenchymal-transition-in-human-lung-epithelial-cells
#18
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/29703973/rna-sequencing-reveals-long-term-effects-of-silver-nanoparticles-on-human-lung-cells
#19
Anda R Gliga, Sebastiano Di Bucchianico, Jessica Lindvall, Bengt Fadeel, Hanna L Karlsson
Despite a considerable focus on the adverse effects of silver nanoparticles (AgNPs) in recent years, studies on the potential long-term effects of AgNPs are scarce. The aim of this study was to explore the effects of AgNPs following repeated low-dose, long-term exposure of human bronchial epithelial cells. To this end, the human BEAS-2B cell line was exposed to 1 µg/mL AgNPs (10 nm) for 6 weeks followed by RNA-sequencing (RNA-Seq) as well as genome-wide DNA methylation analysis. The transcriptomics analysis showed that a substantial number of genes (1717) were differentially expressed following AgNP exposure whereas only marginal effects on DNA methylation were observed...
April 27, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29703175/anti-fibrotic-effects-of-pirfenidone-and-rapamycin-in-primary-ipf-fibroblasts-and-human-alveolar-epithelial-cells
#20
M Molina-Molina, C Machahua-Huamani, V Vicens-Zygmunt, R Llatjós, I Escobar, E Sala-Llinas, P Luburich-Hernaiz, J Dorca, A Montes-Worboys
BACKGROUND: Pirfenidone, a pleiotropic anti-fibrotic treatment, has been shown to slow down disease progression of idiopathic pulmonary fibrosis (IPF), a fatal and devastating lung disease. Rapamycin, an inhibitor of fibroblast proliferation could be a potential anti-fibrotic drug to improve the effects of pirfenidone. METHODS: Primary lung fibroblasts from IPF patients and human alveolar epithelial cells (A549) were treated in vitro with pirfenidone and rapamycin in the presence or absence of transforming growth factor β1 (TGF-β)...
April 27, 2018: BMC Pulmonary Medicine
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