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Epithelial to mesenchymal transition and fibrosis

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https://www.readbyqxmd.com/read/28931214/baicalin-alleviates-radiation-induced-epithelial-mesenchymal-transition-of-primary-type-ii-alveolar-epithelial-cells-via-tgf-%C3%AE-and-erk-gsk3%C3%AE-signaling-pathways
#1
Jinhua Lu, Yazhen Zhong, Zechen Lin, Xianlei Lin, Zhaohui Chen, Xuping Wu, Nan Wang, Haiqiao Zhang, Siyu Huang, Yuan Zhu, Yuanyuan Wang, Shengyou Lin
BACKGROUND: Radiation therapy is commonly used to treat thoracic malignancies. However, it may lead to severe lung pneumonitis and ultimately fibrosis. Irradiation has been reported to increase epithelial-mesenchymal transition (EMT) of type II alveolar epithelial cells (AEC), which play an important role in pulmonary fibrosis. The transforming growth factor-β (TGF-β) and ERK/glycogen synthase kinase 3β (GSK3β) pathways are critically involved in radiation-induced EMT. In the present study, we investigated whether baicalin was a novel therapeutic candidate for radiation-induced EMT in type II AEC...
September 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28926603/scavenging-of-reactive-oxygen-species-by-astaxanthin-inhibits-epithelial-mesenchymal-transition-in-high-glucose-stimulated-mesothelial-cells
#2
Kazuaki Hara, Chieko Hamada, Keiichi Wakabayashi, Reo Kanda, Kayo Kaneko, Satoshi Horikoshi, Yasuhiko Tomino, Yusuke Suzuki
BACKGROUND: High glucose concentrations influence the functional and structural development of the peritoneal membrane. We previously reported that the oral administration of astaxanthin (AST) suppressed peritoneal fibrosis (PF) as well as inhibited oxidative stress, inflammation, and epithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells (PMCs) in a chlorhexidine-induced PF rat model. This suggests that oxidative stress induction of EMT is a key event during peritoneal damage...
2017: PloS One
https://www.readbyqxmd.com/read/28919801/transforming-growth-factor-%C3%AE-1-smad3-independent-epithelial-mesenchymal-transition-in-type-i-collagen-glomerulopathy
#3
Amanda C Brodeur, Anna M Roberts-Pilgrim, Kimberlee L Thompson, Craig L Franklin, Charlotte L Phillips
The glomerulofibrotic Col1a2-deficient mouse model demonstrates glomerular homotrimeric type I collagen deposition in mesangial and subendothelial spaces. In this report, we investigate the role of transforming growth factor β1 (TGF-β1) in myofibroblast activation and epithelial-mesenchymal transition (EMT) in this glomerulopathy. Immunohistochemical analyses of glomerular α-sma, desmin, vimentin, and proliferating cell nuclear antigen demonstrated parietal epithelial cell proliferation and EMT in late stages of the glomerulopathy in the Col1a2-deficient mice...
2017: International Journal of Nephrology and Renovascular Disease
https://www.readbyqxmd.com/read/28919019/epithelial-to-mesenchymal-transition-epigenetic-reprogramming-driving-cellular-plasticity
#4
REVIEW
Nicolas Skrypek, Steven Goossens, Eva De Smedt, Niels Vandamme, Geert Berx
Epithelial-to-mesenchymal transition (EMT) is a process in which epithelial cells lose their junctions and polarity to gain a motile mesenchymal phenotype. EMT is essential during embryogenesis and adult physiological processes like wound healing, but is aberrantly activated in pathological conditions like fibrosis and cancer. A series of transcription factors (EMT-inducing transcription factor; EMT-TF) regulate the induction of EMT by repressing the transcription of epithelial genes while activating mesenchymal genes through mechanisms still debated...
September 14, 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/28918026/anti-fibrotic-effects-of-synthetic-oligodeoxynucleotide-for-tgf-%C3%AE-1-and-smad-in-an-animal-model-of-liver-cirrhosis
#5
Jung-Yeon Kim, Hyun-Jin An, Woon-Hae Kim, Mi-Gyeong Gwon, Hyemin Gu, Yoon-Yub Park, Kwan-Kyu Park
Liver fibrosis is characterized by changes in tissue architecture and extracellular matrix composition. Liver fibrosis affects not only hepatocytes but also the non-parenchymal cells such as hepatic stellate cells (HSCs), which are essential for maintaining an intact liver structure and function. Transforming growth factor β1 (TGF-β1) is a multifunctional cytokine that induces liver fibrosis through activation of Smad signaling pathways. To improve a new therapeutic approach, synthetic TGF-β1/Smad oligodeoxynucleotide (ODN) was used to suppress both TGF-β1 expression and Smad transcription factor using a combination of antisense ODN and decoy ODN...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28901396/effect-of-1-25-oh-2d3-on-high-glucose%C3%A2-induced-autophagy-inhibition-in-peritoneum
#6
Lina Yang, Yi Fan, Xiuli Zhang, Jin Liu, Jianfei Ma
High glucose (HG) may damage the structure and function of the peritoneal membrane, and is considered to be one of the most important factors that leads to peritoneal fibrosis and ultrafiltration failure. Recently, 1,25(OH)2D3, the active form of vitamin D, was demonstrated to protect against epithelial‑mesenchymal transition and fibrosis in peritoneal mesothelium and other organs. Accumulating evidence has suggested that autophagy serves a protective role in certain diseases by regulating cell survival...
August 31, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28900284/mir-503-modulates-epithelial-mesenchymal-transition-in-silica-induced-pulmonary-fibrosis-by-targeting-pi3k-p85-and-is-sponged-by-lncrna-malat1
#7
Weiwen Yan, Qiuyun Wu, Wenxi Yao, Yan Li, Yi Liu, Jiali Yuan, Ruhui Han, Jingjin Yang, Xiaoming Ji, Chunhui Ni
Silicosis is a kind of chronic, progressive and incurable lung fibrotic diseases with largely unknown and complex pathogenesis and molecular mechanisms. Mounting evidence suggests that microRNAs (miRNAs, miRs) are involved in the pathogenesis of silicosis. Our previous study based on miRNA microarray had shown that the expression levels of miR-503 were down-regulated in mouse lung tissues of silica-induced pulmonary fibrosis. Here, we validated the decreased expression of miR-503 in the fibrotic mouse lung tissues, human bronchial epithelial cells (HBE) and human lung adenocarcinoma A549 cells which were exposed to silica...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28895372/-tipping-extracellular-matrix-remodelling-towards-regression-of-liver-fibrosis-novel-concepts
#8
Fernando Magdaleno, Robert Schierwagen, Frank E Uschner, Jonel Trebicka
Fibrosis development was initially conceived as an incessant progressive condition. Nowadays, it has become evident that fibrotic tissue undergoes a continuous two-way process: fibrogenesis and fibrinolysis, characterizing the remodeling of extracellular matrix (ECM). However, in established fibrosis, this two-way process is tipped towards fibrogenesis and this leads to a self-perpetuating accumulation of ECM, a distinct metabolic unit, as well as other cells and processes promoting fibrosis deposition. Several mechanisms promote fibrosis regression, such as degradation of ECM, infiltration of restorative macrophages, prevention of the epithelial-mesenchymal transition of hepatocytes, restoration of the liver sinusoidal endothelial cells' differentiation phenotype, and reversion to quiescence, apoptosis and senescence of hepatic stellate cells (HSC)...
September 11, 2017: Minerva Gastroenterologica e Dietologica
https://www.readbyqxmd.com/read/28891150/endothelial-to-mesenchymal-transition-in-cardiovascular-diseases-developmental-signalling-pathways-gone-awry
#9
REVIEW
Gonzalo Sánchez-Duffhues, Amaya García de Vinuesa, Peter Ten Dijke
The process named endothelial-to-mesenchymal transition (EndMT) was observed for the first time during the development of the chicken embryo several decades ago. Interestingly, accumulating evidence suggests that EndMT plays a critical role in the onset and progression of a multiple postnatal cardiovascular diseases. EndMT is controlled by a set of developmental signalling pathways, very similar to the process of epithelial-to-mesenchymal transition (EMT), which determine the activity of a number of EndMT transcriptional effectors...
September 11, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28883453/%C3%AE-catenin-twist-and-snail-transcriptional-regulation-of-emt-in-smokers-and-copd-and-relation-to-airflow-obstruction
#10
Malik Quasir Mahmood, Eugene Haydn Walters, Shakti D Shukla, Steve Weston, Hans Konrad Muller, Chris Ward, Sukhwinder Singh Sohal
COPD is characterised by poorly reversible airflow obstruction usually due to cigarette smoking. The transcription factor clusters of β-catenin/Snail1/Twist has been implicated in the process of epithelial mesenchymal transition (EMT), an intermediate between smoking and airway fibrosis, and indeed lung cancer. We have investigated expression of these transcription factors and their "cellular localization" in bronchoscopic airway biopsies from patients with COPD, and in smoking and non-smoking controls. An immune-histochemical study compared cellular protein expression of β-catenin, Snail1 and Twist, in these subject groups in 3 large airways compartment: epithelium (basal region), reticular basement membrane (Rbm) and underlying lamina propria (LP)...
September 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28877670/indoleamine-2-3-dioxygenase-ido-increases-during-renal-fibrogenesis-and-its-inhibition-potentiates-tgf-%C3%AE-1-induced-epithelial-to-mesenchymal-transition
#11
Luiz Henrique Gomes Matheus, Gislene Mendes Simão, Taíssa Altieri Amaral, Rodrigo Barbosa Oliveira Brito, Camila Soares Malta, Yves Silva Teles Matos, Alexandre Chagas Santana, Gabriela Gomes Cardoso Rodrigues, Maria Clara Albejante, Erna Elisabeth Bach, Maria Aparecida Dalboni, Cleber Pinto Camacho, Humberto Dellê
BACKGROUND: Indoleamine 2, 3-dioxygenase (IDO) is an immunomodulatory molecule that has been implicated in several biological processes. Although IDO has been linked with some renal diseases, its role in renal fibrosis is still unclear. Because IDO may be modulated by TGF-β1, a potent fibrogenic molecule, we hypothesized that IDO could be involved in renal fibrosis, especially acting in the TGF-β1-induced tubular epithelial-mesenchymal transition (EMT). We analyzed the IDO expression and activity in a model of renal fibrogenesis, and the effect of the IDO inhibitor 1-methyl-tryptophan (MT) on TGF-β1-induced EMT using tubular cell culture...
September 6, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28875950/blocking-posttranslational-core-fucosylation-ameliorates-rat-peritoneal-mesothelial-cell-epithelial-mesenchymal-transition
#12
Long-Kai Li, Nan Wang, Wei-Dong Wang, Xiang-Ning Du, Xin-Yu Wen, Ling-Yu Wang, Yi-Yao Deng, Da-Peng Wang, Hong-Li Lin
Background: Core fucosylation (CF), catalyzed by α-1,6 fucosyltransferase (Fut8) in mammals, plays an important role in pathological processes through posttranslational modification of key signaling receptor proteins, including transforming growth factor (TGF)-β receptors and platelet-derived growth factor (PDGF) receptors. However, its effect on peritoneal fibrosis is unknown. Here, we investigated its influence on epithelial-mesenchymal transition (EMT) of rat peritoneal mesothelial cells (PMCs) in vitro induced by a high-glucose (HG) culture solution...
September 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28873461/interleukin-17-induces-human-alveolar-epithelial-to-mesenchymal-cell-transition-via-the-tgf-%C3%AE-1-mediated-smad2-3-and-erk1-2-activation
#13
Ting Wang, Yuan Liu, Jing-Feng Zou, Zhen-Shun Cheng
Idiopathic pulmonary fibrosis (IPF) is a chronic and usually progressive lung disease and the epithelial-mesenchymal transition (EMT) may play an important role in the pathogenesis of pulmonary fibrosis. IL-17 is a proinflammatory cytokine which promotes EMT profiles in lung inflammatory diseases. In this study, we investigated the effect of IL-17 on EMT in alveolar epithelial cell line A549 and the role of TGFβ1-Smad and ERK signaling pathways in the process. Morphological observation on the cells was performed under inverted microscope...
2017: PloS One
https://www.readbyqxmd.com/read/28872461/fibroblast-specific-inhibition-of-tgf-%C3%AE-1-signaling-attenuates-lung-and-tumor-fibrosis
#14
Ying Wei, Thomas J Kim, David H Peng, Dana Duan, Don L Gibbons, Mitsuo Yamauchi, Julia R Jackson, Claude J Le Saux, Cheresa Calhoun, Jay Peters, Rik Derynck, Bradley J Backes, Harold A Chapman
TGF-β1 signaling is a critical driver of collagen accumulation and fibrotic disease but also a vital suppressor of inflammation and epithelial cell proliferation. The nature of this multifunctional cytokine has limited the development of global TGF-β1 signaling inhibitors as therapeutic agents. We conducted phenotypic screens for small molecules that inhibit TGF-β1-induced epithelial-mesenchymal transition without immediate TGF-β1 receptor (TβR) kinase inhibition. We identified trihydroxyphenolic compounds as potent blockers of TGF-β1 responses (IC50 ~50 nM), Snail1 expression, and collagen deposition in vivo in models of pulmonary fibrosis and collagen-dependent lung cancer metastasis...
September 5, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28859984/epstein-barr-virus-encoded-latent-membrane-protein-1-induces-epithelial-to-mesenchymal-transition-by-inducing-v-set-ig-domain-containing-4-vsig4-expression-via-nf-kb-in-renal-tubular-epithelial-hk-2%C3%A2-cells
#15
Seung-Mi Kim, Se Won Oh, Sang Hyun Park, Dae Young Hur, Seung-Woo Hong, Sang Youb Han
The epithelial to mesenchymal transition (EMT), a hallmark of chronic kidney disease, is a key event in the conversion from tubular epithelial cells to myofibroblasts in renal fibrosis. Epstein-Barr virus (EBV) is a γ-herpes oncovirus associated with chronic kidney disease. However, the relationship between EBV and the EMT process in renal tubular epithelial cells is not well understood. Among EBV-latent genes, EBV-encoded latent membrane protein 1 (LMP1) induces EMT by regulating a variety of molecules in EBV-induced oncogenic transformation...
August 30, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28851916/a-novel-three-dimensional-culture-system-maintaining-the-physiological-extracellular-matrix-of-fibrotic-model-livers-accelerates-progression-of-hepatocellular-carcinoma-cells
#16
Yuya Miyauchi, Kentaro Yasuchika, Ken Fukumitsu, Takamichi Ishii, Satoshi Ogiso, Takahito Minami, Hidenobu Kojima, Ryoya Yamaoka, Hokahiro Katayama, Takayuki Kawai, Elena Yukie Yoshitoshi-Uebayashi, Sadahiko Kita, Katsutaro Yasuda, Naoya Sasaki, Shinji Uemoto
Liver fibrosis is characterized by the progressive accumulation of extracellular matrix (ECM) and is a strong predictor of hepatocellular carcinoma (HCC) development and progression. However, the effect of ECM in fibrotic livers on HCC cells is poorly understood. The aims of this study were to create a new culture system that retained the natural ECM of fibrotic model livers and to establish whether natural ECM regulated the characteristics of HCC cells. Using an organ decellularization technique, we created a new culture system that preserved the tissue-specific ECM of fibrotic model livers from CCl4-treated rats...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28839221/exosomes-from-high-glucose-treated-glomerular-endothelial-cells-trigger-the-epithelial-mesenchymal-transition-and-dysfunction-of-podocytes
#17
Xiaoming Wu, Yanbin Gao, Liping Xu, Wanyu Dang, Huimin Yan, Dawei Zou, Zhiyao Zhu, Liangtao Luo, Nianxiu Tian, Xiaolei Wang, Yu Tong, Zheji Han
New data indicate that abnormal glomerular endothelial cell (GEC)-podocyte crosstalk plays a critical role in diabetic nephropathy (DN). The aim of our study is to investigate the role of exosomes from high glucose (HG)-treated GECs in the epithelial-mesenchymal transition (EMT) and dysfunction of podocytes. In this study, exosomes were extracted from GEC culture supernatants and podocytes were incubated with the GEC-derived exosomes. Here, we demonstrate that HG induces the endothelial-mesenchymal transition (EndoMT) of GECs and HG-treated cells undergoing the EndoMT secrete more exosomes than normal glucose (NG)-treated GECs...
August 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28827139/reduced-glutathione-level-promotes-epithelial-mesenchymal-transition-in-lens-epithelial-cells-via-a-wnt-%C3%AE-catenin-mediated-pathway-relevance-for-cataract-therapy
#18
Zongbo Wei, Jane Caty, Jeremy Whitson, Amy D Zhang, Ramkumar Srinivasagan, Terrance J Kavanagh, Hong Yan, Xingjun Fan
The epithelial-mesenchymal transition (EMT) process plays a pivotal role in the pathogenesis of posterior capsular opacification (PCO) owing to remnant lens epithelial cell proliferation, migration and transformation after cataract surgery. The latter, we hypothesize, may result in posterior capsule wrinkling and opacification due to a profound change in the lens growth environment via a 1000-fold reduction of extracellular glutathione (GSH) levels. To test this hypothesis, we investigated the EMT process in cell culture and GSH biosynthesis deficiency mouse models...
August 18, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28820530/cxcr7-attenuates-the-tgf-%C3%AE-induced-endothelial-to-mesenchymal-transition-and-pulmonary-fibrosis
#19
Shuhong Guan, Jun Zhou
Lung fibrosis is a progressive and often fatal lung disease characterized by fibroblast proliferation and excessive deposition of extracellular matrix in the lungs. The chemokine receptor CXCR7 has been shown to control cell adhesion, migration and proliferation by regulating the epithelial-to-mesenchymal transition (EMT), but the role of CXCR7 in regulating the endothelial-to-mesenchymal transition (EndMT) and lung fibrosis remains largely unclear. In this study, we investigated the interrelation of CXCR7 and TGF-β, a crucial player in lung fibrogenesis...
August 18, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28817830/microrna-200a-inhibits-transforming-growth-factor-%C3%AE-1-induced-proximal-tubular-epithelial-mesenchymal-transition-by-targeting-%C3%AE-catenin
#20
Yi Gong, Zhexue Qin, Baoshang Zhou, Hua Chen, Zhengmin Shi, Jing Zhang
BACKGROUND: The epithelial-mesenchymal transition (EMT) is a crucial event in the development of renal interstitial fibrosis (RIF). A growing body of evidence indicates that β-catenin plays an important role in various types of fibrosis. Although members of the microRNA (miRNA)-200 family have been suggested to suppress EMT in cancer and fibrosis, the function of miRNA-200a in regulating the progression of RIF is unknown. We speculate that miRNA-200a may hinder this progression through the suppression of β-catenin...
August 18, 2017: Nephron
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