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Epithelial to mesenchymal transition and fibrosis

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https://www.readbyqxmd.com/read/28646553/epithelial-mesenchymal-transition-emt-a-spectrum-of-states-role-in-lung-development-homeostasis-and-disease
#1
REVIEW
Mohit Kumar Jolly, Chris Ward, Mathew Suji Eapen, Stephen Myers, Oskar Hallgren, Herbert Levine, Sukhwinder Singh Sohal
Epithelial Mesenchymal Transition (EMT) plays key roles during lung development and many lung diseases such as Chronic Obstructive Pulmonary Disease (COPD), lung cancer and pulmonary fibrosis. Here, integrating morphological observations with underlying molecular mechanisms, we highlight the functional role of EMT in lung development and injury repair, and discuss how it can contribute to pathogenesis of chronic lung disease. We discuss the evidence of manifestation of EMT and its potential driving role in COPD, idiopathic pulmonary fibrosis (IPF), bronchiolitis obliterans syndrome (BOS), and lung cancer, while noting that all cells need not display a full EMT in any of these contexts, i...
June 24, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28646304/ndrg2-knockdown-promotes-fibrosis-in-renal-tubular-epithelial-cells-through-tgf-%C3%AE-1-smad3-pathway
#2
Zhibo Jin, Chaohui Gu, Fengyan Tian, Zhankui Jia, Jinjian Yang
Renal fibrosis is a common pathological pathway of various chronic kidney diseases progressing to end-stage renal disease and is characterized by tubular atrophy, fibroblast/myofibroblast activation and excessive deposition of extracellular matrix (ECM). N-Myc downstream-regulated gene-2 (NDRG2) is reported to be associated with liver fibrosis in rats. However, the biological function of NDRG2 in renal fibrosis remains unclear. Therefore, we investigate the effect of NDRG2 on renal fibrosis and the underlying mechanism of NDRG2 in TGF-β1-induced renal tubular epithelial cells (HK-2)...
June 23, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28638433/shenqiwan-ameliorates-renal-fibrosis-in-rats-by-inhibiting-tgf-%C3%AE-1-smads-signaling-pathway
#3
Hongshu Chen, Yiqing Xu, Yuanxiao Yang, Xiaojie Zhou, Shijie Dai, Changyu Li
Epithelial-mesenchymal transition (EMT) refers to the transition of epithelial cells into mesenchymal cells. Emerging evidence suggests that EMT is a key point in renal interstitial fibrosis (RIF). Traditional Chinese Medicine Shenqiwan (SQW) is widely used in clinical treatment of chronic kidney disease, but the underlying mechanism remains unclear. The purpose of this study is to investigate the effect of SQW on renal fibrosis and its association with TGF-β1/Smads signaling pathway. A rat model of adenine (150 mg/kg) was established and intragastrically treated with various concentrations of SQW at dose of 1...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28636545/reversal-effect-of-jagged1-signaling-inhibition-on-ccl4-induced-hepatic-fibrosis-in-rats
#4
Guiju Tang, Zhihong Weng, Jun Song, Yixiong Chen
The role of the Notch ligand Jagged1 in hepatic fibrosis remains to be elucidated. In the current study, we investigated the role of Jagged1 in the activation of hepatic stellate cells (HSCs) and development of hepatic fibrosis in rats. In vitro, Jagged1 in HSCs was downregulated and upregulated by Jagged1 siRNA and pcDNA3.1 Jagged1, respectively. The levels of epithelial-mesenchymal transition (EMT) markers and HSC activation markers were assessed using western blot analysis. The proliferation and migration capacity of HSCs were assessed using 5-ethynyl-2'-deoxyuridine (EdU) incorporation and Transwell migration assays...
June 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28627612/targeted-inhibition-of-endoplasmic-reticulum-stress-new-hope-for-renal-fibrosis-review
#5
Ben Ke, Na Zhu, Fuli Luo, Yang Xu, Xiangdong Fang
Chronic kidney disease (CKD) has a very high mortality rate and remains a global health challenge. Inhibiting renal fibrosis is one of the most promising therapeutic strategies for CKD. Recent studies have indicated that endoplasmic reticulum stress (ERS) serves an active role in the development of acute and chronic kidney disease, especially with regards to renal fibrosis. In the current review, the authors summarize the latest understanding of the role of ERS during the onset of renal fibrosis. ERS promotes renal fibrosis through multiple signaling pathways, such as transforming growth factor‑β, epithelial‑mesenchymal transition and oxidative stress...
June 13, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28624456/in%C3%A2-vitro-evidences-of-epithelial-to-mesenchymal-transition-in-low-cell-density-cultured-human-fetal-hepatocytes
#6
Cinzia Maria Chinnici, Vitale Miceli, Mariangela Pampalone, Antonio Lo Nigro, Giandomenico Amico, Pier Giulio Conaldi
Culturing fetal hepatocytes in high cell-density allowed stabilization of the hepatocyte phenotype up to 8 weeks, including the maintenance of liver-specific functions. On the other hand, when cultured at low cell-density, fetal hepatocytes underwent morphological modifications and acquired fibroblastic morphology. Since a switch from E-cadherin to vimentin expression accompanied these changes, we hypothesized the occurrence of epithelial-to-mesenchymal transition when fetal hepatocytes were cultured at low cell-density...
June 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28624451/rapamycin-protects-against-paraquat-induced-pulmonary-fibrosis-activation-of-nrf2-signaling-pathway
#7
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/28622289/microrna-26a-and-26b-inhibit-lens-fibrosis-and-cataract-by-negatively-regulating-jagged-1-notch-signaling-pathway
#8
Xiaoyun Chen, Wei Xiao, Weirong Chen, Xialin Liu, Mingxing Wu, Qu Bo, Yan Luo, Shaobi Ye, Yihai Cao, Yizhi Liu
Fibrosis is a chronic process involving development and progression of multiple diseases in various organs and is responsible for almost half of all known deaths. Epithelial-mesenchymal transition (EMT) is the vital process in organ fibrosis. Lens is an elegant biological tool to investigate the fibrosis process because of its unique biological properties. Using gain- and loss-of-function assays, and different lens fibrosis models, here we demonstrated that microRNA (miR)-26a and miR-26b, members of the miR-26 family have key roles in EMT and fibrosis...
June 16, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28621668/blocking-epithelial-to-mesenchymal-transition-in-glioblastoma-with-a-sextet-of-repurposed-drugs-the-eis-regimen
#9
Richard E Kast, Nicolas Skuli, Georg Karpel-Massler, Guido Frosina, Timothy Ryken, Marc-Eric Halatsch
This paper outlines a treatment protocol to run alongside of standard current treatment of glioblastoma- resection, temozolomide and radiation. The epithelial to mesenchymal transition (EMT) inhibiting sextet, EIS Regimen, uses the ancillary attributes of six older medicines to impede EMT during glioblastoma. EMT is an actively motile, therapy-resisting, low proliferation, transient state that is an integral feature of cancers' lethality generally and of glioblastoma specifically. It is believed to be during the EMT state that glioblastoma's centrifugal migration occurs...
June 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28616713/modulation-of-the-tgf-%C3%AE-1-induced-epithelial-to-mesenchymal-transition-emt-mediated-by-p1-and-p2-purine-receptors-in-mdck-cells
#10
Mariachiara Zuccarini, Patricia Giuliani, Silvana Buccella, Valentina Di Liberto, Giuseppa Mudò, Natale Belluardo, Marzia Carluccio, Margherita Rossini, Daniele Filippo Condorelli, Michel Piers Rathbone, Francesco Caciagli, Renata Ciccarelli, Patrizia Di Iorio
Epithelial to mesenchymal transition (EMT) occurs during embryogenesis or under pathological conditions such as hypoxia, injury, chronic inflammation, or tissue fibrosis. In renal tubular epithelial cells (MDCK), TGF-β1 induces EMT by reducing or increasing epithelial or mesenchymal marker expression, respectively. In this study, we confirmed that the cAMP analogues, 8-CPT-cAMP or N6-Ph-cAMP, inhibited the TGF-β1-driven overexpression of the mesenchymal markers ZEB-1, Slug, Fibronectin, and α-SMA. Furthermore, we showed that A1, A2A, P2Y1, P2Y11, and P2X7 purine receptor agonists modulated the TGF-β1-induced EMT through the involvement of PKA and/or MAPK/ERK signaling...
June 14, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28609013/polydatin-alleviated-radiation-induced-lung-injury-through-activation-of-sirt3-and-inhibition-of-epithelial-mesenchymal-transition
#11
Kun Cao, Xiao Lei, Hu Liu, Hainan Zhao, Jiaming Guo, Yuanyuan Chen, Yang Xu, Ying Cheng, Cong Liu, Jianguo Cui, Bailong Li, Jianming Cai, Fu Gao, Yanyong Yang
Radiation-induced lung injury (RILI) is one of the most common and fatal complications of thoracic radiotherapy. It is characterized with two main features including early radiation pneumonitis and fibrosis in later phase. This study was to investigate the potential radioprotective effects of polydatin (PD), which was shown to exert anti-inflammation and anti-oxidative capacities in other diseases. In this study, we demonstrated that PD-mitigated acute inflammation and late fibrosis caused by irradiation. PD treatment inhibited TGF-β1-Smad3 signalling pathway and epithelial-mesenchymal transition...
June 13, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28598023/nintedanib-reduces-ventilation-augmented-bleomycin-induced-epithelial-mesenchymal-transition-and-lung-fibrosis-through-suppression-of-the-src-pathway
#12
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/28596300/clear-cell-renal-cell-carcinoma-is-linked-to-epithelial-to-mesenchymal-transition-and-to-fibrosis
#13
Lea Landolt, Øystein Eikrem, Philipp Strauss, Andreas Scherer, David H Lovett, Christian Beisland, Kenneth Finne, Tarig Osman, Mohammad M Ibrahim, Gro Gausdal, Lavina Ahmed, James B Lorens, Jean Paul Thiery, Tuan Zea Tan, Miroslav Sekulic, Hans-Peter Marti
Clear cell renal cell carcinoma (ccRCC) represents the most common type of kidney cancer with high mortality in its advanced stages. Our study aim was to explore the correlation between tumor epithelial-to-mesenchymal transition (EMT) and patient survival. Renal biopsies of tumorous and adjacent nontumorous tissue were taken with a 16 g needle from our patients (n = 26) undergoing partial or radical nephrectomy due to ccRCC RNA sequencing libraries were generated using Illumina TruSeq(®) Access library preparation protocol and TruSeq Small RNA library preparation kit...
June 2017: Physiological Reports
https://www.readbyqxmd.com/read/28594240/dimethylarginine-dimethylaminohydrolase-1-deficiency-induces-the-epithelial-to-mesenchymal-transition-in-renal-proximal-tubular-epithelial-cells-and-exacerbates-kidney-damage-in-aged-and-diabetic-mice
#14
Linlin Shi, Chenyang Zhao, Hongyun Wang, Tong Lei, Shasha Liu, Jianwei Cao, Zhongbing Lu
AIMS: Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, is mainly degraded by dimethylarginine dimethylaminohydrolase (DDAH). Emerging evidence suggests that plasma ADMA accumulation and DDAH1 activity/expression reduction are linked to chronic kidney disease (CKD) pathology, but the mechanisms remain largely unknown. Here, we examined the role of ADMA/DDAH1 in the epithelial-mesenchymal transition (EMT) of tubular epithelial cells (TECs), an important mechanism for the pathogenesis of renal fibrosis...
June 8, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28593951/preventing-tissue-fibrosis-by-local-biomaterials-interfacing-of-specific-cryptic-extracellular-matrix-information
#15
Christine-Maria Horejs, Jean-Philippe St-Pierre, Juha R M Ojala, Joseph A M Steele, Patricia Barros da Silva, Angela Rynne-Vidal, Stephanie A Maynard, Catherine S Hansel, Clara Rodríguez-Fernández, Manuel M Mazo, Amanda Y F You, Alex J Wang, Thomas von Erlach, Karl Tryggvason, Manuel López-Cabrera, Molly M Stevens
Matrix metalloproteinases (MMPs) contribute to the breakdown of tissue structures such as the basement membrane, promoting tissue fibrosis. Here we developed an electrospun membrane biofunctionalized with a fragment of the laminin β1-chain to modulate the expression of MMP2 in this context. We demonstrate that interfacing of the β1-fragment with the mesothelium of the peritoneal membrane via a biomaterial abrogates the release of active MMP2 in response to transforming growth factor β1 and rescues tissue integrity ex vivo and in vivo in a mouse model of peritoneal fibrosis...
June 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28591554/nlrp3-participates-in-the-regulation-of-emt-in-bleomycin-induced-pulmonary-fibrosis
#16
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/28590921/s100a4-in-cancer-progression-and-metastasis-a-systematic-review
#17
REVIEW
Fei Fei, Jie Qu, Mingqing Zhang, Yuwei Li, Shiwu Zhang
Metastasis is the leading cause of cancer-related death and directly associates with cancer progression, resistance to anticancer therapy, and poor patient survival. Current efforts focusing on the underlying molecular mechanisms of cancer metastasis attract a special attention to cancer researchers. The epithelial-mesenchymal transition is a complex of molecular program during embryogenesis, inflammation, tissue fibrosis, and cancer progression and metastasis. S100A4, an important member of S100 family proteins, functions to increase the tumor progression and metastasis...
May 19, 2017: Oncotarget
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
#18
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/28581456/epigenetic-silencing-of-irf1-dysregulates-type-iii-interferon-responses-to-respiratory-virus-infection-in-epithelial-to-mesenchymal-transition
#19
Jun Yang, Bing Tian, Hong Sun, Roberto P Garofalo, Allan R Brasier
Chronic oxidative injury produced by airway disease triggers a transforming growth factor-β (TGF-β)-mediated epigenetic reprogramming known as the epithelial-mesenchymal transition (EMT). We observe that EMT silences protective mucosal interferon (IFN)-I and III production associated with enhanced rhinovirus (RV) and respiratory syncytial virus (RSV) replication. Mesenchymal transitioned cells are defective in inducible interferon regulatory factor 1 (IRF1) expression by occluding RelA and IRF3 access to the promoter...
June 5, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28579116/sirt3-prevents-angiotensin-ii-induced-renal-tubular-epithelial-mesenchymal-transition-by-ameliorating-oxidative-stress-and-mitochondrial-dysfunction
#20
Ping He, Zhuoming Li, Zhongbao Yue, Hui Gao, Guoshuai Feng, Panxia Wang, Yi Huang, Wenwei Luo, Huiqi Hong, Liying Liang, Shaorui Chen, Peiqing Liu
Silent mating type information regulation 2 homolog 3 (SIRT3) is a major protective mediator that ameliorates oxidative stress and mitochondrial dysfunction, which are associated with the pathogenesis of epithelial-mesenchymal transition (EMT). The present study was aimed to investigate the potential role of SIRT3 in renal tubular EMT both in vitro and in vivo. Firstly, we showed that the expression of SIRT3 was repressed in angiotensin II-induced EMT. SIRT3 deficiency triggered EMT response, while over-expression of SIRT3 attenuated EMT response...
June 1, 2017: Molecular and Cellular Endocrinology
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