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Epithelial to mesenchymal transition and fibrosis

Jingjin Yang, Ting Wang, Yan Li, Wenxi Yao, Xiaoming Ji, Qiuyun Wu, Lei Han, Ruhui Han, Weiwen Yan, Jiali Yuan, Chunhui Ni
Silicosis is an occupational pulmonary fibrosis caused by inhalation of silica (SiO2) and there are no ideal drugs to treat this disease. Earthworm extract (EE), a natural nutrient, has been reported to have anti-inflammatory, antioxidant, and anti-apoptosis effects. The purpose of the current study was to test the protective effects of EE against SiO2-induced pulmonary fibrosis and to explore the underlying mechanisms using both in vivo and in vitro models. We found that treatment with EE significantly reduced lung inflammation and fibrosis and improved lung structure and function in SiO2-instilled mice...
October 24, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
Francesca Bianchini, Silvia Peppicelli, Pierangelo Fabbrizzi, Alessio Biagioni, Benedetta Mazzanti, Gloria Menchi, Lido Calorini, Alberto Pupi, Andrea Trabocchi
Fibrosis is the dramatic consequence of a dysregulated reparative process in which activated fibroblasts (myofibroblasts) and Transforming Growth Factor β1 (TGFβ1) play a central role. When exposed to TGFβ1, fibroblast and epithelial cells differentiate in myofibroblasts; in addition, endothelial cells may undergo endothelial-to-mesenchymal transition (EndoMT) and actively participate to the progression of fibrosis. Recently, the role of αv integrins, which recognize the Arg-Gly-Asp (RGD) tripeptide, in the release and signal transduction activation of TGFβ1 became evident...
October 19, 2016: Molecular and Cellular Biochemistry
Ningning Liu, Lailai Li, Xin Zhu, Zhiqiang Ling, Jianguo Feng, Ying Hu, Yi Wang, Lijun Mou, Yi Wang
Chronic kidney disease (CKD) is a worldwide health problem with growing prevalence in developing countries. Renal tubular epithelial-mesenchymal transition (EMT) is a critical step and key factor in the development of this condition. Renal tubulointerstitial fibrosis is a basic pathological change at the later stages of the disease. Therefore, blocking the development of EMT could be a critical factor in curing CKD. We have established a cell-based high-content screening (HCS) method to identify inhibitors of EMT in human proximal tubular epithelial (HK-2) cells by automatic acquisition and processing of dual-fluorescent labeled images...
October 10, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Bo Zhu, Yumei Chen, Xiaolu Shen, Xishi Liu, Sun-Wei Guo
BACKGROUND: Recently emerging evidence indicates that endometriotic lesions are wounds undergoing repeated tissue injury and repair (ReTIAR), and platelets induce epithelial-mesenchymal transition (EMT), fibroblast-to-myofibroblast transdifferentiation (FMT), leading ultimately to fibrosis. Due to the commonality of cyclic bleeding as in endometriosis, adenomyotic lesions are also wounds that undergo ReTIAR, and we have recently provided evidence corroborating platelet-induced EMT, FMT and fibrogenesis in adenomyosis...
October 10, 2016: Reproductive Biology and Endocrinology: RB&E
Kanna Nagaishi, Yuka Mizue, Takako Chikenji, Miho Otani, Masako Nakano, Naoto Konari, Mineko Fujimiya
Bone marrow-derived mesenchymal stem cells (MSCs) have contributed to the improvement of diabetic nephropathy (DN); however, the actual mediator of this effect and its role has not been characterized thoroughly. We investigated the effects of MSC therapy on DN, focusing on the paracrine effect of renal trophic factors, including exosomes secreted by MSCs. MSCs and MSC-conditioned medium (MSC-CM) as renal trophic factors were administered in parallel to high-fat diet (HFD)-induced type 2 diabetic mice and streptozotocin (STZ)-induced insulin-deficient diabetic mice...
October 10, 2016: Scientific Reports
Ya Wang, Ying Le, Jun-Yu Xue, Zong-Ji Zheng, Yao-Ming Xue
TGF-β1-induced epithelial to mesenchymal transition (EMT) process of tubular epithelial cells plays a leading role in the occurrence and progression of renal fibrosis as seen in diabetic nephropathy (DN). High mobility group AT-hook 2 (HMGA2) is considered to be involved in TGF-β1-mediated EMT via multifactorial mechanisms. Specific microRNAs (miRNAs) are closely associated with EMT, and here we focused on let-7d miRNA as a regulator of HMGA2. This study aims to investigate the effects of HMGA2 on EMT process induced by TGF-β1 using small interfering RNA (siRNA) technique in vitro, and further explore the potential role of let-7d miRNA during renal fibrosis in DN...
October 28, 2016: Biochemical and Biophysical Research Communications
Jin Li, Tamara Riedt, Steven Goossens, Carmen Carrillo García, Sabrina Szczepanski, Maria Brandes, Tim Pieters, Linne Dobrosch, Ines Gütgemann, Natalie Farla, Enrico Radaelli, Paco Hulpiau, Nikhil Mallela, Holger Fröhlich, Roberta La Starza, Caterina Matteucci, Tong Chen, Peter Brossart, Cristina Mecucci, Danny Huylebroeck, Jody J Haigh, Viktor Janzen
Epithelial-to-mesenchymal-transition (EMT) is critical for normal embryogenesis and effective post-natal wound healing, but is also associated with cancer metastasis. SNAIL, ZEB and TWIST families of transcription factors are key modulators of the EMT process, but their precise roles in adult hematopoietic development and homeostasis remain unclear. Here we report that genetic inactivation of Zeb2 results in increased frequency of stem and progenitor subpopulations within the bone marrow (BM) and spleen and that these changes accompany differentiation defects in multiple hematopoietic cell lineages...
September 28, 2016: Blood
Manreet Padwal, Peter J Margetts
Peritoneal fibrosis is one of the major complications occurring in long-term peritoneal dialysis patients as a result of injury. Peritoneal fibrosis is characterized by submesothelial thickening and fibrosis which is associated with a decline in peritoneal membrane function. The myofibroblast has been identified as the key player involved in the development and progression of peritoneal fibrosis. Activation of the myofibroblast is correlated with expansion of the extracellular matrix and changes in peritoneal membrane integrity...
September 2016: Kidney Research and Clinical Practice
Pierre-Olivier Delpech, Raphael Thuillier, Thibault SaintYves, Jerome Danion, Sylvain Le Pape, Edwin S van Amersfoort, Beatrijs Oortwijn, Gilles Blancho, Thierry Hauet
BACKGROUND: Ischemia reperfusion injury (IRI) induced immune response is a critical issue in transplantation. Complement and contact system activation are among its key mechanisms. STUDY DESIGN: We investigated the benefits of pre-reperfusion treatment with recombinant human C1INH (rhC1INH), inhibitor of both complement and contact activation, in a pig model of kidney autotransplantation, subjecting the organ to 60 min warm ischemia prior to 24 h static preservation to maximize damage...
2016: Journal of Translational Medicine
Jianbo Yang, Chao Ding, Xujie Dai, Tengfei Lv, Tingbing Xie, Tenghui Zhang, Wen Gao, Jianfeng Gong, Weiming Zhu, Ning Li, Jieshou Li
BACKGROUND: Intestinal fibrosis is a late complication of pelvic radiotherapy. Epithelial-to-mesenchymal transition (EMT) plays an important role in tissue fibrosis. The aim of this study was to examine the effect of soluble dietary fiber on radiation-induced intestinal EMT and fibrosis in a mouse model. MATERIALS AND METHODS: Apple pectin (4% wt/wt in drinking water) was administered to wild-type and pVillin-Cre-EGFP transgenic mice with intestinal fibrosis induced by a single dose of abdominal irradiation of 10 Gy...
September 22, 2016: JPEN. Journal of Parenteral and Enteral Nutrition
Shuaishuai Shi, Yiqiang Zhang, Wenbin Wen, Yine Zhao, Lin Sun
Peritoneal dialysis (PD)-associated peritoneal fibrosis is a serious complication in patients with chronic renal failure on dialysis maintenance. Studies have shown that patients on long‑term PD have chronic inflammation. The epithelial-to-mesenchymal transition (EMT) induced by inflammation is a major cause of peritoneal fibrosis and dysfunction. As a potent antioxidant property, melatonin has an antifibrotic effect. The present study investigated the effects of melatonin on lipopolysaccharide (LPS)‑induced EMT and examined the molecular mechanisms in peritoneal mesothelial cells using western blotting, reverse transcription‑polymerase chain reaction and immunofluorescence staining...
September 16, 2016: Molecular Medicine Reports
Claire L Donohoe, Joanne Lysaght, Jacintha O'Sullivan, John V Reynolds
There is compelling epidemiological evidence linking obesity to many tumours; however, the molecular mechanisms fuelling this association are not clearly understood. Emerging evidence links changes in the tumour microenvironment with the obese state, and murine and human studies highlight the relevance of adipose stromal cells (ASCs), including immune cells, both at remote fat depots, such as the omentum, as well as in peritumoural tissue. These obesity-associated changes have been implicated in several hallmarks of cancer, including the chronic inflammatory state and associated cell signalling, epithelial-to-mesenchymal transition (EMT), tumour-related fibrosis, angiogenesis, and genomic instability...
September 12, 2016: Trends in Endocrinology and Metabolism: TEM
Malik Q Mahmood, David Reid, Chris Ward, Hans K Muller, Darryl A Knight, Sukhwinder S Sohal, Eugene H Walters
BACKGROUND AND OBJECTIVE: COPD is characterized by poorly reversible airflow obstruction usually due to cigarette smoking. Transforming growth factor (TGF)-β1 has been implicated in the pathogenesis of COPD, and in particular a process called epithelial mesenchymal transition (EMT), which may well be an intermediatory between smoking and both airway fibrosis and lung cancer. The downstream classical or 'canonical' TGF-β1 pathway is via the phosphorylated (p) Smad transcription factor system...
September 11, 2016: Respirology: Official Journal of the Asian Pacific Society of Respirology
Inge Ubink, Elisha R Verhaar, Onno Kranenburg, Roel Goldschmeding
CCN2, also known as connective tissue growth factor (CTGF) is a transcriptional target of TGF-β signaling. Unlike its original name ("CTGF") suggested, CCN2 is not an actual growth factor but a matricellular protein that plays an important role in fibrosis, inflammation and connective tissue remodeling in a variety of diseases, including cancer. In pancreatic ductal adenocarcinoma, CCN2 signaling induces stromal infiltration and facilitates a strong tumor-stromal interaction. In many types of cancer, CCN2 overexpression has been associated with poor outcome...
September 2016: Journal of Cell Communication and Signaling
Yongjun Tang, Ruoxi He, Jian An, Pengbo Deng, Li Huang, Wei Yang
Pulmonary fibrosis, 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 medicable on pancreatic fibrosis and liver fibrosis. However, its role in pulmonary fibrosis has not been reported yet. In the present study, we investigated the hypothesis that H19 play a promotive role in bleomycin-induced epithelial-mesenchymal transition of alveolar epithelial cell, and H19 exerts its effect through miR-29b regulation...
October 21, 2016: Biochemical and Biophysical Research Communications
Agnieszka Loboda, Mateusz Sobczak, Alicja Jozkowicz, Jozef Dulak
Renal fibrosis, irrespective of its etiology, is a final common stage of almost all chronic kidney diseases. Increased apoptosis, epithelial-to-mesenchymal transition, and inflammatory cell infiltration characterize the injured kidney. On the molecular level, transforming growth factor-β1 (TGF-β1)-Smad3 signaling pathway plays a central role in fibrotic kidney disease. Recent findings indicate the prominent role of microRNAs, small noncoding RNA molecules that inhibit gene expression through the posttranscriptional repression of their target mRNAs, in different pathologic conditions, including renal pathophysiology...
2016: Mediators of Inflammation
Jang-Hee Cho, Hye-Myung Ryu, Eun-Joo Oh, Ju-Min Yook, Ji-Sun Ahn, Hee-Yeon Jung, Ji-Young Choi, Sun-Hee Park, Yong-Lim Kim, Ihm Soo Kwak, Chan-Duck Kim
Alpha1-antitrypsin (AAT) exerts its anti-inflammatory effect through regulating the activity of serine proteinases. This study evaluated the inhibitory effects of AAT against the transforming growth factor (TGF)-β1 induced epithelial-to-mesenchymal transition (EMT) in unilateral ureter obstruction (UUO) mice and Madin-Darby canine kidney (MDCK) cells. C57BL/6 mice with induced UUO were injected intraperitoneally with AAT (80 mg/Kg) or vehicle for 7 days. MDCK cells were treated with TGF-β1 (2 ng/mL) for 48 hours to induce EMT, and co-treated with AAT (10 mg/mL) to inhibit the EMT...
2016: PloS One
Masashi Kawami, Rika Harabayashi, Mioka Miyamoto, Risako Harada, Ryoko Yumoto, Mikihisa Takano
PURPOSE: Methotrexate (MTX) therapy of certain cancers and rheumatoid arthritis often induces serious interstitial lung complications including pulmonary fibrosis. In this study, we investigated the epithelial-mesenchymal transition (EMT) induced by MTX and by transforming growth factor (TGF)-β1 in the human alveolar epithelial cell line A549 in order to develop new strategies for the prevention of EMT. METHODS: First, we examined the effect of TGF-β1 and MTX on cell morphology and the expression of EMT-related mRNAs in A549 cells...
September 7, 2016: Lung
Yun Xiao, Jishi Liu, Yu Peng, Xuan Xiong, Ling Huang, Huixiang Yang, Jian Zhang, Lijian Tao
Tubular epithelial-mesenchymal transition (EMT) has been widely accepted as the underlying mechanisms of renal interstitial fibrosis (RIF). The production of reactive oxygen species (ROS) plays a vital role in tubular EMT process. The purpose of this study was to investigate the involved molecular mechanisms in TGF-beta-induced EMT and identify the potential role of glutathione S-transferase alpha 3 (GSTA3) in this process. The iTRAQ screening was performed to identify protein alterations of the rats underwent unilateral-ureteral obstruction (UUO)...
2016: PloS One
Jianjian Zheng, Fujun Yu, Peihong Dong, Limei Wu, Yuan Zhang, Yanwei Hu, Lei Zheng
Epithelial-mesenchymal transition (EMT) process is considered as a key event in the activation of hepatic stellate cells (HSCs). Hedgehog (Hh) pathway is known to be required for EMT process. Long non-coding RNAs (lncRNAs) have been reported to be involved in a wide range of biological processes. Plasmacytoma variant translocation 1 (PVT1), a novel lncRNA, is often up-regulated in various human cancers. However, the role of PVT1 in liver fibrosis remains undefined. In this study, PVT1 was increased in fibrotic liver tissues and activated HSCs...
August 30, 2016: Oncotarget
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