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Abdul Soofi, Katherine I Wolf, Margo P Emont, Nathan Qi, Gabriel Martinez-Santibanez, Edward Grimley, Wesam Ostwani, Gregory R Dressler
Obesity and its associated complications, such as insulin resistance and non-alcoholic fatty liver disease, are reaching epidemic proportions. In mice, the TGF-beta superfamily is implicated in the regulation of white and brown adipose tissue differentiation. The Kielin/chordin-like Protein (KCP) is a secreted regulator of the TGF-beta superfamily pathways that can inhibit both TGF-beta and activin signals while enhancing bone morphogenetic protein (BMP) signaling. However, KCP's effects on metabolism and obesity have not been studied in animal models...
April 19, 2017: Journal of Biological Chemistry
Nagat Frara, Paul W Fisher, Yingjie Zhao, Joseph T Tarr, Mamta Amin, Steven N Popoff, Mary F Barbe
Transforming growth factor beta 1 (TGFbeta-1) and connective tissue growth factor (CCN2) are important mediators of tissue repair and fibrosis, with CCN2 functioning as a downstream mediator of TGFβ-1. Substance P (SP) is also linked to collagen production in tenocytes. A link between SP, TGFbeta-1 and CCN2 has yet to be established in tenocytes or fibrogenic processes. We sought to determine whether SP induces tenocyte proliferation, CCN2, or collagen production via TGFbeta-1 signaling or independently in rat primary tenocytes...
March 1, 2017: Connective Tissue Research
Marcelo Maia Pinheiro, Caroline Lais Stoppa, Claudete Justina Valduga, Cristina Eunice Okuyama, Renata Gorjão, Regina Mara Silva Pereira, Susana Nogueira Diniz
Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of anti-diabetic agents that are widely used in clinical practice to improve glycemic control in patients with type 2 diabetes. DPP-4 is also known as lymphocyte cell surface protein, CD26, and plays an important role in T-cell immunity. Recent studies suggest that DPP-4 inhibitors improve beta-cell function and attenuate autoimmunity in type 1 diabetic mouse models. To investigate the direct effect of DPP4 in immune response, human peripheral blood mononuclear cells (PBMC) from healthy volunteers were obtained by Ficoll gradient and cultivated in the absence (control) or presence of phytohemagglutinin (PHA), or stimulated with PHA and treated with sitagliptin...
March 30, 2017: European Journal of Pharmaceutical Sciences
Maria D Castellone, Mikko O Laukkanen
Activation of resting fibroblasts to myofibroblasts characterizes several physiological and pathological conditions, from wound healing to aggressive metastatic cancers. In tissue damage, including wound healing, fibroblasts are activated in response to injury for a limited period of time to stimulate the healing process. Similar biological mechanisms are maintained in pathological conditions, e.g., scleroderma and cancer, where myofibroblasts persist in producing cytokines and growth factors to drive the development of fibrosis and the progression of disease...
January 1, 2017: Frontiers in Bioscience (Scholar Edition)
Hardik R Mody, Sau Wai Hung, Mohammad AlSaggar, Jazmine Griffin, Rajgopal Govindarajan
The identification of epigenetic reversal agents for use in combination chemotherapies to treat human pancreatic ductal adenocarcinomas (PDAC) remains an unmet clinical need. Pharmacologic inhibitors of Enhancer of Zeste Homolog 2 (EZH2) are emerging as potential histone methylation reversal agents for the treatment of various solid tumors and leukemia; however, the surprisingly small set of mRNA targets identified with EZH2 knockdown suggests novel mechanisms contribute to their antitumorigenic effects. Here, 3-deazaneplanocin-A (DZNep), an inhibitor of S-adenosyl-L-homocysteine hydrolase and EZH2 histone lysine-N-methyltransferase, significantly reprograms noncoding microRNA (miRNA) expression and dampens TGFβ1-induced epithelial-to-mesenchymal (EMT) signals in pancreatic cancer...
November 2016: Molecular Cancer Research: MCR
Yi Wang, Guanying Han, Bin Guo, Jianhua Huang
BACKGROUND: Hyaluronan (also known as hyaluronic acid) oligosaccharides (O-HA) can promote angiogenesis and wound healing; however, there are few reports on whether O-HA also plays a role in healing wounds of diabetic patients. METHODS: In this study, we prepared a special ointment containing a mixture of hyaluronan fragments from 2 to 10 disaccharide units and investigated its effects on healing the wounds of diabetic rats. RESULTS: We found that O-HA significantly increases proliferation, migration, and tube formation of endothelial cells under high glucose conditions, and topical administration of O-HA ointment promotes wound healing by increasing angiogenesis in the wounded area of the skin...
December 2016: Pharmacological Reports: PR
Dong Li, Hui Sun, Wen-Jing Sun, Hong-Bo Bao, Shu-Han Si, Jia-Lin Fan, Ping Lin, Rong-Jun Cui, Yu-Jia Pan, Si-Min Wen, Xiu-Lan Zheng, Xiao-Guang Yu
EMT (epithelial-mesenchymal transition) occurs in a wide range of tumor types, and has been shown to be crucial for metastasis. Epigenetic modifications of histones contribute to chromatin structure and result in the alterations in gene expression. Tri-methylation of histone H3 lysine 4 (H3K4me3) is associated with the promoters of actively transcribed genes and can serve as a transcriptional on/off switch. RbBP5 is a component of the COMPASS/ -like complex, which catalyzes H3K4me3 formation. In this study, we found that in the process of TGF-Beta1 induced EMT in the prostate cancer cell line DU145, H3K4me3 enrichment and RbBP5 binding increased in the vicinity of Snail (SNAI1) transcription start site...
October 4, 2016: Oncotarget
Bangrong Cao, Lin Feng, Dan Lu, Yan Liu, Yu Liu, Suping Guo, Naijun Han, Xiangyang Liu, Yousheng Mao, Jie He, Shujun Cheng, Yanning Gao, Kaitai Zhang
It is hypothesized that the molecular status in negative surgical margin (NSM) is associated with prognosis of cancer patients. In this study, the prognostic relevance of Epithelial-to-Mesenchymal Transition (EMT) molecular events in NSMs in patients with NSCLC was investigated. EMT model was developed, in which the mesenchymal transition of human immortalized bronchial epithelial cell line was induced by TGF-beta1. Gene expression of EMT-induced cells and NSMs from 60 lung squamous cell carcinoma (SCC) patients was profiled by microarray and validated by quantitative RT-PCR...
July 29, 2016: Oncotarget
W-C Guo, X-F He, Y-H Li, Z-H Li, Q-L Mei, Y Chen
OBJECTIVE: This study aimed to build VX2 liver tumor model in rabbits and to investigate the sequential transcatheter arterial chemoembolization (TACE) and portal vein embolizations (PVE) vs. TACE or PVE alone on rabbit VX2 liver carcinoma and liver regeneration. MATERIALS AND METHODS: VX2 liver tumor models were built in the rabbit. Rabbits carrying VX2 liver tumors were divided into four groups, including TACE+PVE, TACE, PVE and Sham groups respectively. Hematoxylin and eosin (HE) staining was performed to visualize the structures of tumor tissues...
July 2016: European Review for Medical and Pharmacological Sciences
E Peterová, A Mrkvicová, L Podmolíková, M Řezáčová, J Kanta
Rat liver myofibroblasts (MFB) are the key cells involved in the deposition of extracellular matrix in fibrotic liver. They were isolated by repeated passaging of non-parenchymal cell fraction and cultured in 3-dimensional (3D) collagen gel mimicking tissue. The transfer of MFB from plastic dishes to collagen resulted in the change in their shape from large and spread to slender with long extensions. The expression of transforming growth factor-beta1 (TGF-beta1) and of MFB markers, alpha-smooth muscle actin (alpha-SMA) and cellular fibronectin (EDA-FN), on protein level was significantly decreased in collagen gel...
November 8, 2016: Physiological Research
L Zhang, L Yan, M Cao, H Zhang, C Li, Y Bai, P Yu, M Li, X Zhao
OBJECTIVE: To investigate the impact of sperm-associated antigen 9 (SPAG9) on proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in endometrial cancer. MATERIALS AND METHODS: The present authors' previous study demonstrated that SPAG9 is highly expressed in endometrial cancer tissues. They analyzed correlation between the levels of SPAG9 and mRNA of EMT-related genes in endometrial carcinoma tissue by using quantitative real-time PCR...
2016: European Journal of Gynaecological Oncology
Pedro Serralheiro, Elisa Cairrão, Cláudio J Maia, Marina João, Carlos M Costa Almeida, Ignacio Verde
OBJECTIVES: Transforming growth factor-beta1 (TGF-β1) may participate in local chronic inflammatory processes in varicose veins and in venous wall structure modifications through regulation of matrix metalloproteinases (MMP) and their inhibitors (tissue inhibitor of metalloproteinase (TIMP)). The aim of this study was to analyze the effect of TGF-β1 in the vein wall, namely on the gene expression of selected MMP, TIMP and TGF-β1 receptors. METHODS: Healthy vein samples were harvested from eight subjects who underwent coronary bypass graft surgery with great saphenous vein...
June 20, 2016: Phlebology
Rodica Bălaşa, Smaranda Maier, Septimiu Voidăzan, Adina Huţanu, Zoltán Bajkó, Anca Moţăţăianu, Brindusa Tilea, Cristina Tiu
Individual response to interferon beta (IFN-β) 1a treatment is heterogeneous in multiple sclerosis (MS). Our objective was to find a connection between serum levels of interleukin (IL)-10, IL-17 and transforming growth factor beta (TGF-β)1 in MS patients treated with IFN-β in order to identify the nonresponders (NR). MATERIAL AND METHODS: We included in the study 32 healthy subjects and 32 MS patients: 10 naive, 10 early treated and 12 late treated with INF-β1a. Serum determination of cytokines and brain MRI were performed at the beginning of the study, after 6 and 12 months...
June 15, 2016: CNS & Neurological Disorders Drug Targets
Ying Jin, Yuwan Li, Chenghao Zhang, Shuhong Wu, Daixiong Cheng, Yi Liu
OBJECTIVE: To discuss whether human amniotic mesenchymal stem cells (hAMSCs) possesses the characteristic of mesenchymal stem cells, and could differentiate into ligament cells in vitro after induction. METHODS: The hAMSCs were separated through enzyme digestion, and the phenotypic characteristics of hAMSCs were tested through flow cytometry. The cells at passage 3 were cultured with L-DMEM/F12 medium containing transforming growth factor beta1 (TGF-beta1) + basic fibroblast growth factor (bFGF) (group A), containing hyaluronic acid (HA) (group B), containing TGF-beta1+bFGF+HA (group C), and simple L-DMEM/F12 medium (group D) as control group...
February 2016: Chinese Journal of Reparative and Reconstructive Surgery
John Martin, Adam Midgley, Soma Meran, Emma Woods, Timothy Bowen, Aled O Phillips, Robert Steadman
Fibroblasts are central to wound healing and fibrosis through TGFβ1-triggered differentiation into contractile, α-smooth muscle actin (α-SMA)-positive myofibroblasts. This is mediated by accumulation of a pericellular matrix of hyaluronan (HA) and the HA-dependent co-localization of CD44 with the epidermal growth factor receptor (EGFR). Interactions of HA with hyaladherins, such as inter-α-inhibitor (IαI) and tumor necrosis factor-stimulated gene-6 (TSG-6), are also essential for differentiation. This study investigated the mechanisms involved...
June 24, 2016: Journal of Biological Chemistry
Zhou-xin Ren, Hai-bin Yu, Jian-sheng Li, Jun-ling Shen, Jun-kai Li, Shan Luo
In the study, the effects of Panax notoginseng saponins (PNS) on alveolar epithelial to mesenchymal transition (EMT) and extracellular matrix degradation were observed in a type of human alveolar epithelial cell, A549 cells, stimulated by TGF-beta1. Firstly, MTT method was applied to evaluation of cellular proliferation and found that PNS from 12.5 mg x L(-1) to 200 mg x L(-1) dosage could not inhibit significantly cellular proliferation. Then, cells were divided into five groups, normal group, TGF-beta1 group, TGF-beta1 + 50 mg x L(-1) PNS group, TGF-beta1 + 100 mg x L(-1) PNS group and TGF-beta1 + 200 mg x L(-1) PNS group...
December 2015: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Shilpa Maria, Venkatesh V Kamath, Krishnanand Satelur, Komali Rajkumar
CONTEXT: Oral submucous fibrosis (OSF) is a potentially malignant oral disorder causally linked to the habit of chewing arecanut. The pathogenesis of the disorder is multifactorial and transforming growth factor beta (TGF-beta) is a prominent player in the induction of fibrosis. The alkaloids of the arecanut seem to target the TGF-beta and the deposition of collagen is predominantly mediated through this cytokine. AIMS AND OBJECTIVES: The present study attempts to induce OSF in Sprague-Dawley rats by injections with solutions of arecanut and pan masala extracts...
January 2016: Journal of Cancer Research and Therapeutics
M Ganesh Kamath, C Ganesh Pai, Asha Kamath, Annamma Kurien
BACKGROUND: Diagnostic parameters that can predict the presence of chronic pancreatitis (CP) in patients with recurrent pain due to pancreatitis would help to direct appropriate therapy. This study aimed to compare the serum levels of monocyte chemoattractant protein-1 (MCP-1), transforming growth factor-beta1 (TGF-beta1), nerve growth factor (NGF), resistin and hyaluronic acid (HA) in patients with recurrent acute pancreatitis (RAP) and CP to assess their ability to differentiate the two conditions...
April 2016: Hepatobiliary & Pancreatic Diseases International: HBPD INT
Justin Rustenhoven, Miranda Aalderink, Emma L Scotter, Robyn L Oldfield, Peter S Bergin, Edward W Mee, E Scott Graham, Richard L M Faull, Maurice A Curtis, Thomas I-H Park, Mike Dragunow
BACKGROUND: Transforming growth factor beta 1 (TGFβ1) is strongly induced following brain injury and polarises microglia to an anti-inflammatory phenotype. Augmentation of TGFβ1 responses may therefore be beneficial in preventing inflammation in neurological disorders including stroke and neurodegenerative diseases. However, several other cell types display immunogenic potential and identifying the effect of TGFβ1 on these cells is required to more fully understand its effects on brain inflammation...
February 11, 2016: Journal of Neuroinflammation
Xin Li, Da-yong Li, Wen-na Chen, Yang Zhang, Bao-qing Liu, Shi-zheng Li, Jun-jie Hou
OBJECTIVE: To explore the effect of arteriosclerosis obliterans (ASO) blood stasis syndrome (BSS) serum on vascular endothelial cell injury and to study the regulation of Taohong Siwu Decoction (TSD) on it. METHODS: Umbilical vein endothelial cell culture system was established. The serum endothelial cell injury model with ASO BSS was prepared. Low, medium, and high concentrations TSD containing serums were respectively added. The endothelial cell proliferation activity was observed by MTT method...
November 2015: Chinese Journal of Integrated Traditional and Western Medicine
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