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Epithelial to mesenchymal transition and fibrosis

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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
#1
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
#2
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
#3
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
#4
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...
December 19, 2016: 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
#5
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
#6
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)...
February 3, 2017: Gene
https://www.readbyqxmd.com/read/28159470/hedgehog-pathway-plays-a-vital-role-in-hiv-induced-epithelial-mesenchymal-transition-of-podocyte
#7
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...
January 31, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28131417/mir-18a-5p-inhibits-sub-pleural-pulmonary-fibrosis-by-targeting-tgf-%C3%AE-receptor-ii
#8
Qian Zhang, Hong Ye, Fei Xiang, Lin-Jie Song, Li-Ling Zhou, Peng-Cheng Cai, Jian-Chu Zhang, Fan Yu, Huan-Zhong Shi, Yunchao Su, Jian-Bao Xin, Wan-Li Ma
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease that typically leads to respiratory failure and death within 3-5 years of diagnosis. Sub-pleural pulmonary fibrosis is a pathological hallmark of IPF. Bleomycin treatment of mice is a an established pulmonary fibrosis model. We recently showed that bleomycin-induced epithelial-mesenchymal transition (EMT) contributes to pleural mesothelial cell (PMC) migration and sub-pleural pulmonary fibrosis. MicroRNA (miRNA) expression has recently been implicated in the pathogenesis of IPF...
January 25, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28127848/mir-30c-protects-diabetic-nephropathy-by-suppressing-epithelial-to-mesenchymal-transition-in-db-db-mice
#9
Yanru Zhao, Zhongwei Yin, Huaping Li, Jiahui Fan, Shenglan Yang, Chen Chen, Dao Wen Wang
Epithelial-to-mesenchymal transition (EMT) plays a significant role in tubulointerstitial fibrosis, which is a hallmark of diabetic nephropathy. Thus, identifying the mechanisms of EMT activation could be meaningful. In this study, loss of miR-30c accompanied with increased EMT was observed in renal tubules of db/db mice and cultured HK2 cells exposed to high glucose. To further explore the roles of miR-30c in EMT and tubulointerstitial fibrosis, recombinant adeno-associated viral vector was applied to manipulate the expression of miR-30c...
January 27, 2017: Aging Cell
https://www.readbyqxmd.com/read/28123498/allicin-inhibits-tubular-epithelial-myofibroblast-transdifferentiation-under-high-glucose-conditions-in-vitro
#10
Hong Huang, Fenping Zheng, Xuehong Dong, Fang Wu, Tianfeng Wu, Hong Li
Previous studies have suggested that tubular epithelial-mesenchymal transition (EMT) is an important event in renal tubulointerstitial fibrosis, which is a clinical characteristic of diabetic nephropathy. The present study aimed to investigate the effect of allicin, the major biological active component of garlic, on the EMT of a human renal proximal tubular epithelial cell line (HK-2) cultured under high glucose concentrations. HK-2 cells were exposed for 48 h to 5.5 or 25 mmol/l D-glucose, 25 mmol/l D-glucose plus allicin (2...
January 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28115235/anti-fibrotic-effects-of-chronic-treatment-with-the-selective-fxr-agonist-obeticholic-acid-in-the-bleomycin-induced-rat-model-of-pulmonary-fibrosis
#11
Paolo Comeglio, Sandra Filippi, Erica Sarchielli, Annamaria Morelli, Ilaria Cellai, Francesca Corcetto, Chiara Corno, Elena Maneschi, Alessandro Pini, Luciano Adorini, Gabriella Barbara Vannelli, Mario Maggi, Linda Vignozzi
Farnesoid X receptor (FXR) activation by obeticholic acid (OCA) has been demonstrated to inhibit inflammation and fibrosis development in liver, kidney and intestine in multiple disease models. FXR activation has also been demonstrated to suppress the inflammatory response and to promote lung repair after lung injury. This study investigated the protective effects of OCA treatment (3 or 10mg/kg/day) on inflammation, tissue remodeling and fibrosis in the bleomycin-induced pulmonary fibrosis rat model. Effects of OCA treatment on morphological and molecular alterations of the lung, as well as remodeling of the alveoli and the right ventricle were also evaluated...
January 20, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28112996/snail-slug-yap-taz-complexes-cooperatively-regulate-mesenchymal-stem-cell-function-and-bone-formation
#12
Yi Tang, Stephen J Weiss
Snail and Slug are zinc-finger transcription factors that play key roles in directing the epithelial-mesenchymal transition (EMT) programs associated with normal development as well as disease progression. More recent work suggests that these EMT-associated transcription factors also modulate the function of both embryonic and adult stem cells. Interestingly, YAP and TAZ, the co-transcriptional effectors of the Hippo pathway, likewise play an important role in stem cell self-renewal and lineage commitment. While direct intersections between the Snail/Slug and Hippo pathways have not been described previously, we recently described an unexpected cooperative interaction between Snail/Slug and YAP/TAZ that controls the self-renewal and differentiation properties of bone marrow-derived mesenchymal stem cells (MSCs), a cell population critical to bone development...
January 23, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28111379/knocking-down-tcf8-inhibits-high-glucose-and-angiotensin-ii-induced-epithelial-to-mesenchymal-transition-in-podocytes
#13
Changhuan Bai, Shumei Liang, Yunshan Wang, Bo Jiao
Epithelial to mesenchymal transition (EMT) is a physiological phenomenon in mammalian embryogenesis by which epithelial cells become mesenchymal stem cells. Studies have indicated that an inappropriate EMT plays a key role in a variety of pathogenic processes such as embryonic development and tumor metastasis. Moreover, recent studies have indicated EMT also plays an important role in renal fibrosis. In the current study, glucose and angiotensin II promoted EMT in podocytes as well as changes in the cellular morphology of podocytes...
January 22, 2017: Bioscience Trends
https://www.readbyqxmd.com/read/28099883/beta2-adrenergic-signaling-affects-the-phenotype-of-human-cardiac-progenitor-cells-through-emt-modulation
#14
Francesca Pagano, Francesco Angelini, Camilla Siciliano, Julia Tasciotti, Giorgio Mangino, Elena De Falco, Roberto Carnevale, Sebastiano Sciarretta, Giacomo Frati, Isotta Chimenti
Human cardiac progenitor cells (CPCs) offer great promises to cardiac cell therapy for heart failure. Many in vivo studies have shown their therapeutic benefits, paving the way for clinical translation. The 3D model of cardiospheres (CSs) represents a unique niche-like in vitro microenvironment, which includes CPCs and supporting cells. CSs have been shown to form through a process mediated by epithelial-to-mesenchymal transition (EMT). β2-Adrenergic signaling significantly affects stem/progenitor cells activation and mobilization in multiple tissues, and crosstalk between β2-adrenergic signaling and EMT processes has been reported...
January 15, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28092863/adipose-derived-stem-cells-ameliorate-renal-interstitial-fibrosis-through-inhibition-of-emt-and-inflammatory-response-via-tgf-%C3%AE-1-signaling-pathway
#15
Yan Song, Changliang Peng, Shasha Lv, Jing Cheng, Shanshan Liu, Qing Wen, Guangju Guan, Gang Liu
Adipose-derived stem cells (ADSCs) have been successfully used to treat acute kidney injury or acute renal failure. However, the effect of ADSCs on treating renal interstitial fibrosis remains unknown. Here, we assessed the therapeutic efficacy of ADSCs on renal interstitial fibrosis induced by unilateral ureter obstruction (UUO) and explored the potential mechanisms. After 7days of UUO, rats were injected with ADSCs (5×10(6)) or vehicle via tail vein. We found that ADSCs administration significantly ameliorated renal interstitial fibrosis, the occurrence of epithelial-mesenchymal transition (EMT) and inflammatory response...
January 13, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28077319/role-of-insulin-like-growth-factor-axis-in-the-bleomycin-induced-lung-injury-in-rats
#16
Lakshmi Kanth Kotarkonda, Ritu Kulshrestha, Krishnan Ravi
BACKGROUND: Alveolar epithelial cell injury has been proposed as a causative factor for the onset and progression of pulmonary fibrosis. However, the role of type II alveolar epithelial cells (AECs) in the epithelial mesenchymal transition (EMT) is controversial. AIMS: The present study performed in rats instilled with bleomycin investigated a) the expressions of the insulin growth factor (IGF-1) and insulin growth factor binding protein 5 (IGFBP-5) and transforming growth factor (TGF-β1) in the type II AECs, b) the role of type II AECs in EMT and extracellular matrix (ECM) formation and, c) the effect of pioglitazone on all the above parameters...
January 7, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28064160/specific-heparanase-inhibition-reverses-glucose-induced-mesothelial-to-mesenchymal-transition
#17
Valentina Masola, Simona Granata, Gloria Bellin, Giovanni Gambaro, Maurizio Onisto, Carlo Rugiu, Antonio Lupo, Gianluigi Zaza
BACKGROUND: Epithelial-to-mesenchymal transition (EMT) of peritoneal mesothelial cells induced by high glucose (HG) levels is a major biological mechanism leading to myofibroblast accumulation in the omentum of patients on peritoneal dialysis (PD). Heparanase (HPSE), an endoglycosidase that cleaves heparan sulfate chains, is involved in the EMT of several cell lines, and may have a major role in this pro-fibrotic process potentially responsible for the failure of dialysis. Its specific inhibition may therefore plausibly minimize this pathological condition...
January 7, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28060321/imaging-of-cell-shape-alteration-and-cell-movement-in-drosophila-gastrulation-using-de-cadherin-reporter-transgenic-flies
#18
M Rezaul Karim, Tomohiro Haruta, Taro Matsumoto, Hiroki Oda, Hiroaki Taniguchi
Gastrulation is the first set of morphologically dynamic events that occur during the embryonic development of multicellular animals such as Drosophila. This morphological alteration is also recognized as epithelial to mesenchymal transition (EMT). Dysregulation of EMT is associated with fibrosis and cancer metastasis. There is emerging evidence that EMT is controlled by a number of molecular mechanisms. As such, many key genes that control apical constriction are also known to be important factors in the EMT observed in cancer metastasis...
December 29, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27997892/the-role-of-tlr4-in-m1-macrophage-induced-epithelial-mesenchymal-transition-of-peritoneal-mesothelial-cells
#19
Jun Shi, Qing Li, Meixiao Sheng, Min Zheng, Manshu Yu, Lu Zhang
BACKGROUND/AIMS: Peritoneal fibrosis is a frequent complication of peritoneal dialysis that follows inflammation. It is recognized that epithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells (PMCs), plays a key role in fibrogenesis. However, the relationship between inflammatory macrophages and PMCs remains elusive. In this study, we investigated the effects of different polarized macrophages on EMT of HMrSV5 PMCs. METHODS: Monocytes were polarized to M1/M2 macrophages before being added to HMrSV5 in direct or indirect contact...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27989784/emodin-suppresses-tgf-%C3%AE-1-induced-epithelial-mesenchymal-transition-in-alveolar-epithelial-cells-through-notch-signaling-pathway
#20
Rundi Gao, Ruilin Chen, Yu Cao, Yuan Wang, Kang Song, Ya Zhang, Junchao Yang
Pulmonary fibrosis is characterized by the destruction of lung tissue architecture and the formation of fibrous foci, currently has no satisfactory treatment. Emodin is a component of Chinese herb that has been reported to be medicament on pancreatic fibrosis and liver fibrosis. However, its role in pulmonary fibrosis has not been established yet. In the present study, we investigated the hypothesis that Emodin plays an inhibitory role in TGF-β1 induced epithelial-mesenchymal transition (EMT) of alveolar epithelial cell, and Emodin exerts its effect through the Notch signaling pathway...
March 1, 2017: Toxicology and Applied Pharmacology
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