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Epithelial to mesenchymal transition and fibrosis

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https://www.readbyqxmd.com/read/28315789/involvement-of-epithelial-mesenchymal-transition-afforded-by-activation-of-lox-1-tgf-%C3%AE-1-klf6-signaling-pathway-in-diabetic-pulmonary-fibrosis
#1
Xiao-Zhou Zou, Zhi-Cheng Gong, Ting Liu, Fang He, Tian-Tian Zhu, Dai Li, Wei-Fang Zhang, Jun-Lin Jiang, Chang-Ping Hu
BACKGROUND AND OBJECTIVE: Diabetic pulmonary fibrosis is a severe disease that increases mortality risk of diabetes. However, the molecular mechanisms leading to pulmonary fibrosis in diabetes are poorly understood. This study investigated the roles of epithelial-mesenchymal transition (EMT) and the associated molecular mechanisms in streptozotocin (STZ)-induced rat pulmonary fibrosis. METHODS: The rat model of diabetic pulmonary fibrosis was established by intraperitoneal injection of a single dose of STZ (35 mg/kg)...
March 15, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28315692/role-of-epithelial-mesenchymal-transition-emt-and-fibroblast-function-in-cerium-oxide-nanoparticles-induced-lung-fibrosis
#2
Jane Ma, Bridget Bishoff, R R Mercer, Mark Barger, Diane Schwegler-Berry, Vincent Castranova
The emission of cerium oxide nanoparticles (CeO2) from diesel engines, using cerium compounds as a catalyst to lower the diesel exhaust particles, is a health concern. We have previously shown that CeO2 induced pulmonary inflammation and lung fibrosis. The objective of the present study was to investigate the modification of fibroblast function and the role of epithelial-mesenchymal transition (EMT) in CeO2-induced fibrosis. Male Sprague-Dawley rats were exposed to CeO2 (0.15 to 7mg/kg) by a single intratracheal instillation and sacrificed at various times post-exposure...
March 15, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28300665/grape-seed-extract-ameliorates-bleomycin-induced-mouse-pulmonary-fibrosis
#3
Qi Liu, Jun-Xia Jiang, Ya-Nan Liu, Yan Guan, Wei Zhao, Yong-Liang Jia, Xin-Wei Dong, Yun Sun, Qiang-Min Xie
Pulmonary fibrosis is common in a variety of inflammatory lung diseases, such as interstitial pneumonia, chronic obstructive pulmonary disease, and silicosis. There is currently no effective clinical drug treatment. It has been reported that grape seed extracts (GSE) has extensive pharmacological effects with minimal toxicity. Although it has been found that GSE can improve the lung collagen deposition and fibrosis pathology induced by bleomycin in rat, its effects on pulmonary function, inflammation, growth factors, matrix metalloproteinases and epithelial-mesenchymal transition remain to be researched...
March 11, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28299674/the-emerging-roles-of-runx-transcription-factors-in-epithelial-mesenchymal-transition
#4
Dominic Chih-Cheng Voon, Jean Paul Thiery
Epithelial-mesenchymal transition (EMT) is an evolutionary conserved morphogenetic program necessary for the shaping of the body plan during development. It is guided precisely by growth factor signaling and a dedicated network of specialised transcription factors. These are supported by other transcription factor families serving auxiliary functions during EMT, beyond their general roles as effectors of major signaling pathways. EMT transiently induces in epithelial cells mesenchymal properties, such as the loss of cell-cell adhesion and a gain in cell motility...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28285699/pirfenidone-plays-a-biphasic-role-in-inhibition-of-epithelial-mesenchymal-transition-in-non-small-cell-lung-cancer
#5
Ayako Fujiwara, Yasushi Shintani, Soichiro Funaki, Tomohiro Kawamura, Toru Kimura, Masato Minami, Meinoshin Okumura
INTRODUCTION: Epithelial to mesenchymal transition (EMT) relates to both organ fibrosis and malignant behavior of cancer. Pirfenidone (PFD) is an anti-fibrotic agent for idiopathic pulmonary fibrosis and one of its functions may be to inhibit fibrotic EMT. This study aimed to investigate the possibility that PFD might exert an anti-tumor effect through inhibition of EMT in non-small cell lung cancer (NSCLC) cell lines in vitro and in vivo. METHODS: NSCLC cells (A549, NCI-H358) were used to evaluate PFD effects on TGF-β1 induced phenotypic changes...
April 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28274525/epithelial-and-endothelial-cell-plasticity-in-chronic-obstructive-pulmonary-disease-copd
#6
REVIEW
Sukhwinder Singh Sohal
Chronic Obstructive Pulmonary Disease (COPD) is mainly caused by smoking and presents with shortness of breath that is progressive and irreversible. It is a worldwide health problem and the fourth most common cause of chronic disability and mortality (even in developed countries). It is a complex disease involving both the airway and lung parenchyma. Small-airway fibrosis is the main contributor to physiological airway dysfunction in COPD. One potential mechanism contributing to small-airway fibrosis is epithelial mesenchymal transition (EMT)...
March 2017: Respiratory Investigation
https://www.readbyqxmd.com/read/28260014/baicalin-ameliorates-renal-fibrosis-via-inhibition-of-transforming-growth-factor-%C3%AE-1-production-and-downstream-signal-transduction
#7
Long Zheng, Chao Zhang, Long Li, Chao Hu, Mushuang Hu, Niyazi Sidikejiang, Xuanchuan Wang, Miao Lin, Ruiming Rong
Previous studies have demonstrated the potential antifibrotic effects of baicalin in vitro, via examination of 21 compounds isolated from plants. However, its biological activity and underlying mechanisms of action in vivo remain to be elucidated. The present study aimed to evaluate the effect of baicalin on renal fibrosis in vivo, and the potential signaling pathways involved. A unilateral ureteral obstruction (UUO)‑induced renal fibrosis model was established using Sprague‑Dawley rats. Baicalin was administrated intraperitoneally every 2 days for 10 days...
February 16, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28259823/evaluation-of-permeability-alteration-and-epithelial-mesenchymal-transition-induced-by-transforming-growth-factor-%C3%AE-1-in-a549-nci-h441-and-calu-3-cells-development-of-an-in-vitro-model-of-respiratory-epithelial-cells-in-idiopathic-pulmonary-fibrosis
#8
Kohei Togami, Kotaro Yamaguchi, Sumio Chono, Hitoshi Tada
INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease, which is accompanied by changes in lung structure. With regard to treatment, aerosolized drugs administered intrapulmonarily are rapidly distributed into the plasma and do not remain in the lungs due to damage to the alveolar epithelium that occurs from pulmonary fibrosis. In this study, we sought to develop an in vitro model of respiratory epithelial cells in IPF for the evaluation of the intrapulmonary distribution of aerosolized drugs...
March 1, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28244647/activation-of-wnt-%C3%AE-catenin-signalling-is-required-for-tgf-%C3%AE-smad2-3-signalling-during-myofibroblast-proliferation
#9
Liang Xu, Wen-Hui Cui, Wen-Cheng Zhou, De-Lin Li, Liu-Cheng Li, Ping Zhao, Xiao-Ting Mo, Zhihui Zhang, Jian Gao
Fibrosis in animal models and human diseases is associated with aberrant activation of the Wnt/β-catenin pathway. Despite extensive research efforts, effective therapies are still not available. Myofibroblasts are major effectors, responsible for extracellular matrix deposition. Inhibiting the proliferation of the myofibroblast is crucial for treatment of fibrosis. Proliferation of myofibroblasts can have many triggering effects that result in fibrosis. In recent years, the Wnt pathway has been studied as an underlying factor as a primary contributor to fibrotic diseases...
February 28, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28239354/matrix-metalloproteinases-7-and-kidney-fibrosis
#10
REVIEW
Ben Ke, Chuqiao Fan, Liping Yang, Xiangdong Fang
Matrix metalloproteinase-7 (MMP-7) is a secreted zinc- and calcium-dependent endopeptidase that degrades a broad range of extracellular matrix substrates and additional substrates. MMP-7 playsa crucial role in a diverse array of cellular processes and appears to be a key regulator of fibrosis in several diseases, including pulmonary fibrosis, liver fibrosis, and cystic fibrosis. In particular, the relationship between MMP-7 and kidney fibrosis has attracted significant attention in recent years. Growing evidence indicates that MMP-7 plays an important role in the pathogenesis of kidney fibrosis...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28223370/the-lim-only-protein-fhl2-is-a-negative-regulator-of-tgf-%C3%AE-1-expression
#11
Jennifer Dahan, Florence Levillayer, Tian Xia, Yann Nouët, Catherine Werts, Martine Fanton d'Andon, Minou Adib-Conquy, Anne-Marie Cassard-Doulcier, Varun Khanna, Ju Chen, Thierry Tordjmann, Marie-Annick Buendia, Grégory Jouvion, Yu Wei
TGF-β1 is a master cytokine in many biological processes including tissue homeostasis, epithelial to mesenchymal transition and wound repair. Here we report that the four and a half LIM-only protein 2 (FHL2) is a critical regulator of TGF-β1 expression. Devoid of DNA-binding domain, FHL2 is a transcriptional co-factor that plays the role of co-activator or co-repressor depending on the cell and promoter contexts. We detected association of FHL2 with the TGF-β1 promoter, which showed higher activity in Fhl2(-/-) cells than WT cells in a reporter assay...
February 21, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28220242/expression-of-clonorchis-sinensis-giiispla2-protein-in-baculovirus-infected-insect-cells-and-its-overexpression-facilitating-epithelial-mesenchymal-transition-in-huh7-cells-via-akt-pathway
#12
Mei Shang, Zhizhi Xie, Zeli Tang, Lei He, Xiaoyun Wang, Caiqin Wang, Yinjuan Wu, Ye Li, Lu Zhao, Zhiyue Lv, Zhongdao Wu, Yan Huang, Xinbing Yu, Xuerong Li
Although prior studies confirmed that group III secretory phospholipase A2 of Clonorchis sinensis (CsGIIIsPLA2) had stimulating effect on liver fibrosis by binding to LX-2 cells, large-scale expression of recombinant protein and its function in the progression of hepatoma are worth exploring. Because of high productivity and low lipopolysaccharides (LPS) in the Sf9-baculovirus expression system, we firstly used this system to express the coding region of CsGIIIsPLA2. The molecular weight of recombinant CsGIIIsPLA2 protein was about 34 kDa...
February 20, 2017: Parasitology Research
https://www.readbyqxmd.com/read/28215221/targeting-chromatin-remodeling-in-inflammation-and-fibrosis
#13
J Yang, B Tian, A R Brasier
Mucosal surfaces of the human body are lined by a contiguous epithelial cell surface that forms a barrier to aerosolized pathogens. Specialized pattern recognition receptors detect the presence of viral pathogens and initiate protective host responses by triggering activation of the nuclear factor κB (NFκB)/RelA transcription factor and formation of a complex with the positive transcription elongation factor (P-TEFb)/cyclin-dependent kinase (CDK)9 and Bromodomain-containing protein 4 (BRD4) epigenetic reader...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28207769/role-of-glycogen-synthase-kinase-3%C3%AE-and-ppar-%C3%AE-on-epithelial-to-mesenchymal-transition-in-dss-induced-colorectal-fibrosis
#14
Jacopo Di Gregorio, Roberta Sferra, Silvia Speca, Antonella Vetuschi, Caroline Dubuquoy, Pierre Desreumaux, Simona Pompili, Loredana Cristiano, Eugenio Gaudio, Vincenzo Flati, Giovanni Latella
BACKGROUND: Intestinal fibrosis is characterized by abnormal production and deposition of extracellular matrix (ECM) proteins by activated myofibroblasts. The main progenitor cells of activated myofibroblasts are the fibroblasts and the epithelial cells, the latter through the epithelial-mesenchymal transition (EMT). AIM: To evaluate the action of the new PPAR-γ modulator, GED-0507-34 Levo (GED) on the expression of EMT associated and regulatory proteins such as TGF-β, Smad3, E-cadherin, Snail, ZEB1, β-catenin, and GSK-3β, in a mouse model of DSS-induced intestinal fibrosis...
2017: PloS One
https://www.readbyqxmd.com/read/28203261/curcumin-suppresses-intestinal-fibrosis-by-inhibition-of-ppar%C3%AE-mediated-epithelial-mesenchymal-transition
#15
Su Xu, Bin Jiang, Hui Wang, Cunsi Shen, Hao Chen, Li Zeng
Intestinal fibrotic stricture is a major complication of Crohn's disease (CD) and epithelial-to-mesenchymal transition (EMT) is considered as an important contributor to the formation of intestinal fibrosis by increasing extracellular matrix (ECM) proteins. Curcumin, a compound derived from rhizomes of Curcuma, has been demonstrated with a potent antifibrotic effect. However, its effect on intestinal fibrosis and the potential mechanism is not completely understood. Here we found that curcumin pretreatment significantly represses TGF-β1-induced Smad pathway and decreases its downstream α-smooth muscle actin (α-SMA) gene expression in intestinal epithelial cells (IEC-6); in contrast, curcumin increases expression of E-cadherin and peroxisome proliferator-activated receptor γ (PPARγ) in IEC-6...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28198987/the-content-of-mucin-muc-2-3-and-4-antigens-in-the-bronchial-mucosa-membrane-of-chronic-obstructive-pulmonary-disease-patients-during-acute-exacerbation-initial-report
#16
Svetlana Kovalenko, Andrey Dorofieiev
INTRODUCTION: Changes in mucin production and dyscrinia are common features of inflammation in chronic obstructive pulmonary disease (COPD). Immunohistochemical assessment of MUC-2, MUC-3, MUC-4 expression in the integumentary epithelium, goblet cells, the epithelium of mucous glands and stroma fusiform cells of the bronchial mucosa of COPD patients during an infectious and noninfectious exacerbation was performed. MATERIAL AND METHODS: 30 patients with stage III COPD were enrolled to the study...
2017: Adv Respir Med
https://www.readbyqxmd.com/read/28182573/amplified-canonical-transforming-growth-factor-%C3%AE-signalling-via-heat-shock-protein-90-in-pulmonary-fibrosis
#17
Zaneta Sibinska, Xia Tian, Martina Korfei, Baktybek Kojonazarov, Janina Susanne Kolb, Walter Klepetko, Djuro Kosanovic, Malgorzata Wygrecka, Hossein Ardeschir Ghofrani, Norbert Weissmann, Friedrich Grimminger, Werner Seeger, Andreas Guenther, Ralph T Schermuly
Interstitial lung fibroblast activation coupled with extracellular matrix production is a pathological signature of idiopathic pulmonary fibrosis (IPF), and is governed by transforming growth factor (TGF)-β/Smad signalling. We sought to define the role of heat shock protein (HSP)90 in profibrotic responses in IPF and to determine the therapeutic effects of HSP90 inhibition in a murine model of pulmonary fibrosis.We investigated the effects of HSP90 inhibition in vitro by applying 17-AAG (17-allylamino-17-demethoxygeldanamycin) to lung fibroblasts and A549 cells and in vivo by administering 17-DMAG (17-dimethylaminoethylamino-17-demethoxygeldanamycin) to mice with bleomycin-induced pulmonary fibrosis...
February 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28174691/beta-catenin-participates-in-dialysate-induced-peritoneal-fibrosis-via-enhanced-peritoneal-cell-epithelial-to-mesenchymal-transition
#18
Shuiyu Ji, Hao Deng, Wei Jin, Pengpeng Yan, Rending Wang, Lisha Pang, Jingyi Zhou, Jiaming Zhang, Xiaoying Chen, Xiang Zhao, Jia Shen
Long-term exposure to peritoneal dialysate with high glucose (HG) leads to peritoneal fibrosis and thus decreases dialysis efficiency. In this study, we explored the role of β-catenin in this process. C57BL/6 mice received daily intraperitoneal injection with 10% of the body weight of saline (control), 4.25% glucose peritoneal dialysis fluid (PDF), or PDF combined with 5 mg·kg(-1) of the β-catenin inhibitor ICG-001 (PDF+ICG) for 30 days. Also, mice peritoneal epithelial cells (mPECs) were cultured in 4.25% glucose (HG) or combined with 10 μm ICG-001 (HG+ICG) for 48 h...
February 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28167142/molecular-landscape-of-arthrofibrosis-microarray-and-bioinformatic-analysis-of-the-temporal-expression-of-380-genes-during-contracture-genesis
#19
Mark E Morrey, Matthew P Abdel, Scott M Riester, Amel Dudakovic, Andre J van Wijnen, Bernard F Morrey, Joaquin Sanchez-Sotelo
PURPOSE: Inflammatory changes are suspected in the pathophysiology of arthrofibrosis formation and require early molecular examination. Here, we assessed the hypothesis that early inflammatory genes are related to arthrofibrosis by ascertaining gene expression during the early stages of contracture genesis in an animal model. METHODS: Joint trauma was incited surgically in a cohort of rabbits (n=36) knees followed by immobilization in a model of contracture. Six groups of 6 rabbits were sacrificed at multiple time points (0, 6, 12, 24, 72h and 2weeks)...
April 30, 2017: Gene
https://www.readbyqxmd.com/read/28159470/hedgehog-pathway-plays-a-vital-role-in-hiv-induced-epithelial-mesenchymal-transition-of-podocyte
#20
Xiqian Lan, Hongxiu Wen, Kang Cheng, Andrei Plagov, Seyedeh Shadafarin Marashi Shoshtari, Ashwani Malhotra, Pravin C Singhal
HIV-associated nephropathy (HIVAN) is characterized by heavy proteinuria, rapidly progressive renal failure, and distinct morphological features in the kidney. HIV-induced epithelial-mesenchymal transition (EMT) is critically important for the progression of kidney injury. In this study, we tested the role of hedgehog pathway in the HIV-induced EMT and fibrosis of kidney. We used the Tg26 mice, the abundantly used HIVAN mouse model, to investigate the activation of hedgehog pathway by HIV. Western blotting and real time PCR results showed that renal tissue expression of hedgehog pathway related molecules, including hedgehog homologous (Shh, Ihh, Dhh), PTCH, and Gli1, were increased in HIVAN (Tg26) mice; while immunofluorescent staining displayed localization PTCH expression in podocytes...
March 15, 2017: Experimental Cell Research
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