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Marco De Santis Puzzonia, Angela Maria Cozzolino, Germana Grassi, Francesca Bisceglia, Raffaele Strippoli, Giulia Guarguaglini, Franca Citarella, Benedetto Sacchetti, Marco Tripodi, Alessandra Marchetti, Laura Amicone
In all mammals, the adult liver shows binucleated as well as mononucleated polyploid hepatocytes. The hepatic polyploidization starts after birth with an extensive hepatocyte binucleation and generates hepatocytes of several ploidy classes. While the functional significance of hepatocyte polyploidy is becoming clearer, how it is triggered and maintained needs to be clarified. Aim of this study was to identify a major inducer of hepatocyte binucleation/polyploidization and the cellular and molecular mechanisms involved...
2016: PloS One
Stefano Soldano, Carmen Pizzorni, Sabrina Paolino, Amelia Chiara Trombetta, Paola Montagna, Renata Brizzolara, Barbara Ruaro, Alberto Sulli, Maurizio Cutolo
BACKGROUND: Alternatively activated (M2) macrophages are phenotypically characterized by the expression of specific markers, mainly macrophage scavenger receptors (CD204 and CD163) and mannose receptor-1 (CD206), and participate in the fibrotic process by over-producing pro-fibrotic molecules, such as transforming growth factor-beta1 (TGFbeta1) and metalloproteinase (MMP)-9. Endothelin-1 (ET-1) is implicated in the fibrotic process, exerting its pro-fibrotic effects through the interaction with its receptors (ETA and ETB)...
2016: PloS One
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...
November 2016: Molecular Cancer Research: MCR
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
Shengzheng Luo, Zhenghong Li, Mingyi Xu, Qingqing Zhang, Ying Qu, Lungen Lu
OBJECTIVE: To investigate the role of TGF-beta1 and STAT3 signaling in liver fibrosis using a rat model system and to determine the therapeutic mechanism of AG490 in relation to this signaling pathway. METHODS: Rats were randomly divided into a control group and DENA-induced liver fibrosis model group, and then subdivided into AG490 treatment groups. During fibrosis development, liver tissue samples were collected at different time points (0, 4 and 8 weeks) and evaluated according to the Scheuer scoring system...
December 2015: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
Fanli Meng, Blaise Forrester-Gauntlett, Pavla Turner, Harold Henderson, Björn Oback
The inner cell mass (ICM) of mammalian blastocysts consists of pluripotent epiblast and hypoblast lineages, which develop into embryonic and extraembryonic tissues, respectively. We conducted a chemical screen for regulators of epiblast identity in bovine Day 8 blastocysts. From the morula stage onward, in vitro fertilized embryos were cultured in the presence of cell-permeable small molecules targeting nine principal signaling pathway components, including TGFbeta1, BMP, EGF, VEGF, PDGF, FGF, cAMP, PI3K, and JAK signals...
December 2015: Biology of Reproduction
Susanne Proksch, Gido Bittermann, Kirstin Vach, Roland Nitschke, Pascal Tomakidi, Elmar Hellwig
Human mesenchymal stem cells (hMSCs) are promising candidates for regenerative periodontal strategies, due to the broad spectrum of supportive effects on cells and tissues at the site of application. Although positive effects are visible, the understanding of their underlying mechanisms still requires further elucidation. Recently, we have shown that hMSCs are capable to prompt osteogenic differentiation of alveolar osteoblasts, thereby presumably contributing to alveolar bone regeneration. Another issue that is critical in this context is the attraction of hard tissue-forming cells to regeneration sites, but it is an open question whether hMSCs can afford this...
October 2015: Stem Cells
Dan Li, Xiao-Wei Zhang, Xing-Quan Jiang, Yong-Jie Yin, Zhe Fan, Cheng-Bo Sun, Xing-Hai Chen, Yan-Hui Li, Ke-Xiang Liu
BACKGROUND: This study was designed to evaluate the protective effects of thalidomide on paraquat (PQ)-induced lung injuries in a rat model and to explore the underlying mechanisms. METHODS: Rats were exposed to 50 mg/kg PQ by oral gavage, and treated with thalidomide through oral administration at 60 mg/kg once a day, 6 days/week for 2 weeks. Serum levels of IL-6, TNF-alpha, TGFbeta1 and COL1A1 were detected at different time points after paraquat exposure...
2015: Journal of Inflammation
Kinga Musiał, Agnieszka Bargenda, Danuta Zwolińska
CONTEXT: Epithelial-mesenchymal transition (EMT) leads to renal fibrosis and chronic kidney disease (CKD). OBJECTIVE: The aim of this study was to assess the usefulness of survivin, E-cadherin and metalloproteinases (MMPs) as biomarkers of CKD-related complications. MATERIAL AND METHODS: Survivin, E-cadherin, MMP-2, MMP-9 and TGFbeta1 were assessed by ELISA in 41 children with CKD stages 3 to 5 and in 23 controls. RESULTS: The serum and urine values of analyzed parameters were significantly elevated in CKD patients versus controls and correlated with each other...
2015: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
Kinga Musiał, Agnieszka Bargenda, Danuta Zwolińska
BACKGROUND: Transforming growth factor (TGF)beta1 and matrix metalloproteinases (MMPs) play an essential role in CKD-related tissue remodeling. However, there are no data on urine MMPs and their extracellular inducer EMMPRIN in CKD patients. The aim of study was to assess the concentrations of MMP-2, MMP-7, MMP-9, EMMPRIN and TGFbeta1 in serum and urine of CKD children and to analyze the potential relations between those parameters. METHODS: Forty-one pre-dialysis CKD children and 23 age-matched controls were enrolled in the study...
July 2015: Renal Failure
Jun Liu, Jian Cao, Xiaokun Zhao
BACKGROUND: Distant metastasis is the major cause of cancer-related death, and epithelial-to-mesenchymal transition (EMT) has a critical role in this process. Accumulating evidence indicates that EMT can be regulated by microRNAs (miRNAs). miR-221, as oncogenes in several human cancers, was significantly up-regulated in bladder cancers. However, the role of miR-221 in the progression of bladder cancer metastasis remains largely unknown. METHODS: We used qRT-PCR and western blot to accurately measure the levels of miR-221, STMN1 and EMT markers in TGFβ1 induced EMT of bladder cancer cells...
2015: BMC Urology
O F Gordeeva
TGFP3 family factors play an important role in regulating the balance of self-renewal and differentiation of mouse and human pluripotent stem and embryonic teratocarcinoma cells. The expression patterns of TGFbeta family signaling ligands and functional roles of these signaling pathways differ significantly in mouse and human embryonic stem cells, but the activity and functional role of these factors in mouse and human embryonic teratocarcinoma cells were not sufficiently investigated. Comparative quantitative real-time PCR analysis of the expression of TGF@[beta] family factors in mouse embryonic stem, embryonic germ, and embryonic teratocarcinoma cells showed that embryonic teratocarcinoma cells express lower ActivinA than pluripotent stem cells but similar levels of factors Nodal, Lefty 1, TGFbeta1, BMP4, and GDF3...
July 2014: Ontogenez
Kota Matsuki, Catherine K Hathaway, Albert S Chang, Oliver Smithies, Masao Kakoki
PURPOSE OF REVIEW: It is well established that blocking the renin-angiotensin-aldosterone system (RAAS) is effective for the treatment of cardiovascular and renal complications in hypertension and diabetes mellitus. Although the induction of transforming growth factor beta1 (TGFbeta1) by components of the RAAS mediates the hypertrophic and fibrogenic changes in cardiovascular-renal complications, it is still controversial as to whether TGFbeta1 can be a target to prevent such complications...
March 2015: Current Opinion in Nephrology and Hypertension
Wei Zhang, Xiaoming Dai, Hong Yu, Luyan Wang, Shihui Sun, Junfeng Li, Yusen Zhou
OBJECTIVE: To construct a dual-reporter gene system that will be applicable for use as a tool to screen and evaluate therapeutic drug compounds that inhibit transcription of the gene encoding collagen I, chain at1 (COL1A1). METHODS: The full-length eDNA of transforming growth factor beta1 (TGFbeta1) was cloned by RT-PCR and inserted into two vectors, pcDNA3.1 and pJW4303, for construction of two eukaryotic expression vectors, pcDNA3.1-TGFbeta1 and pJW4303-TGFbeta1...
October 2014: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
Amiq Gazdhar, Iwona Grad, Luca Tamò, Mathias Gugger, Anis Feki, Thomas Geiser
INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible fibrotic lung disease, resulting in respiratory insufficiency and reduced survival. Pulmonary fibrosis is a result of repeated alveolar epithelial microinjuries, followed by abnormal regeneration and repair processes in the lung. Recently, stem cells and their secretome have been investigated as a novel therapeutic approach in pulmonary fibrosis. We evaluated the potential of induced pluripotent stem cells (iPSC) conditioned media (iPSC-cm) to regenerate and repair the alveolar epithelium in vitro and improve bleomycin induced lung injury in vivo...
2014: Stem Cell Research & Therapy
Shuping Zhou, Zhilong Huang, Jiguang Ma, Jingjing Xu, Jinglong Cai, Xianlei Zong, Le Du
OBJECTIVE: To investigate the effect of epidermal stem cells from human hypertrophic scar (HS-ESCs) on the skin wound healing in nude mice. METHODS: 40 mice were randomly divided into two groups as experimental group (n = 20) and control group (n = 20). Wounds, 1 cm in diameters, were made on every mouse back. The wounds were treated with HS-ESCs and erythromycin ointment in experimental group, or only with erythromycin ointment in control group. The wound healing was observed during the following 14 days...
July 2014: Zhonghua Zheng Xing Wai Ke za Zhi, Zhonghua Zhengxing Waike Zazhi, Chinese Journal of Plastic Surgery
Lili Chen, Jennifer Xiao, Junya Kuroda, Tetsuro Ago, Junichi Sadoshima, Richard A Cohen, XiaoYong Tong
Vascular endothelial cells (ECs) are responsible for post-ischemic angiogenesis, a process that is regulated by reactive oxygen species. Recent studies indicate that endothelial Nox4 based NADPH oxidase may have a key role. This study examines the role of endothelial Nox4 in ischemia-induced angiogenesis and explores the potential mechanisms involved. Mouse lines overexpressing human Nox4 wild type (EWT) or its dominant negative form P437H (EDN) specifically in the endothelium were used. Non-transgenic littermate mice (NTg) were used as controls...
December 2014: Biochimica et Biophysica Acta
L A Shpagina, Mm I Voevoda, O S Kotova, V N Maksimov, P S Orlov, I S Shpagin
The article deals with data on association of SNP rs1828591 of HHIP gene with COLD development under exposure to dust and chemical factors. SNP rs1800470 of TGFbeta1 gene is associated with occupational COLD under exposure to dust and did not show connection with COLD under exposure to chemical aerosols. No association was seen between SNP rs4129267 of IL-6R gene and SNP rs1051730 of CHRNA3 gene with occupational COLD under exposure to the studied factors. SNP rs1828591 of HHIP gene is associated with occupational COLD development under exposure to dust and chemical factors...
2014: Meditsina Truda i Promyshlennaia Ekologiia
Franziska Berger, Helene Geddert, Gerhard Faller, Martin Werner, Arno Dimmler
PURPOSE: Increasing evidence indicates that TGFbeta- and EGFR-signaling is involved in the pathogenesis of keratoacanthoma (KA) and squamous cell carcinoma (SCC) of the skin. We analyzed the expression pattern of TGFbeta-signaling components and screened for mutations in tgfbetaR1, egfr, kras and braf in KAs and SCCs. METHODS: Immunohistochemical analysis of TGFbeta1, TGFbetaR1, TGFbetaR2 and phospho-SMAD2/3 was performed on skin tumors (29 KAs, 30 well and 31 moderately differentiated SCCs)...
September 2014: Pathology, Research and Practice
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