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https://www.readbyqxmd.com/read/28337662/a83-01-inhibits-tgf-%C3%AE-induced-upregulation-of-wnt3-and-epithelial-to-mesenchymal-transition-in-her2-overexpressing-breast-cancer-cells
#1
Yanyuan Wu, Trinh Tran, Sami Dwabe, Marianna Sarkissyan, Juri Kim, Miguel Nava, Sheilah Clayton, Richard Pietras, Robin Farias-Eisner, Jaydutt V Vadgama
PURPOSE: The aim of this study is to investigate the mechanisms of interactions between TGF-β and Wnt/β-catenin pathways that induce and regulate EMT and promote breast cancer cells to become resistant to treatment. METHODS: The effect of TGF-β on Wnt/β-catenin signaling pathway was examined by using a human Wnt/β-catenin-regulated cDNA plate array and western blot analysis. The interaction of Twist at promoter of Wnt3 was examined by chromatin immunoprecipitation (ChIP) assay...
March 23, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28331417/%C3%AE-tocotrienol-inhibits-tgf-%C3%AE-1-induced-contractile-phenotype-expression-of-human-airway-smooth-muscle-cells
#2
Takehito Fukushima, Akira Yamasaki, Tomoya Harada, Hiroki Chikumi, Masanari Watanabe, Ryota Okazaki, Miki Takata, Yasuyuki Hasegawa, Jun Kurai, Masaaki Yanai, Akihiro Yamamoto, Yuriko Sueda, Andrew J Halayko, Eiji Shimizu
BACKGROUND: Tocotrienols, members of the vitamin E family, exist in four different isoforms (α, β, γ and δ tocotrienol) that have can be protective against brain damage, as well as having anticancer effects in vivo and in vitro. We have shown that γ-tocotrienol inhibits human airway smooth muscle cell proliferation and migration induced by platelet-derived growth factor (PDGF)-BB by suppressing RhoA activation. In this study, we tested whether γ-tocotrienol modulates transforming growth factor (TGF) -β-induced induction of human airway smooth muscle (ASM) into a contractile phenotype and concomitant synthesis of extracellular matrix proteins...
March 2017: Yonago Acta Medica
https://www.readbyqxmd.com/read/28327634/scleraxis-is-required-for-maturation-of-tissue-domains-for-proper-integration-of-the-musculoskeletal-system
#3
Yuki Yoshimoto, Aki Takimoto, Hitomi Watanabe, Yuji Hiraki, Gen Kondoh, Chisa Shukunami
Scleraxis (Scx) is a basic helix-loop-helix transcription factor that is expressed persistently in tendons/ligaments, but transiently in entheseal cartilage. In this study, we generated a novel Scx(Cre) knock-in (KI) allele, by in-frame replacement of most of Scx exon 1 with Cre recombinase (Cre), to drive Cre expression using Scx promoter and to inactivate the endogenous Scx. Reflecting the intensity and duration of endogenous expression, Cre-mediated excision occurs in tendinous and ligamentous tissues persistently expressing Scx...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28324043/reduced-transforming-growth-factor-beta-activity-in-the-endometrium-of-women-with-heavy-menstrual-bleeding
#4
J A Maybin, L Boswell, V J Young, W C Duncan, Hod Critchley
Context: Heavy menstrual bleeding (HMB) is common and incapacitating. Aberrant menstrual endometrial repair may result in HMB. The TGFβ superfamily contributes to tissue repair, but its role in HMB is unknown. Objective: We hypothesised that TGFβ1 is important for endometrial repair and women with HMB have aberrant TGFβ1 activity at menses. Participants/Setting: Endometrial biopsies were collected from women and menstrual blood loss objectively measured (HMB >80ml/cycle, normal menstrual bleeding, NMB <80ml)...
January 3, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28320972/sensing-relative-signal-in-the-tgf-%C3%AE-smad-pathway
#5
Christopher L Frick, Clare Yarka, Harry Nunns, Lea Goentoro
How signaling pathways function reliably despite cellular variation remains a question in many systems. In the transforming growth factor-β (Tgf-β) pathway, exposure to ligand stimulates nuclear localization of Smad proteins, which then regulate target gene expression. Examining Smad3 dynamics in live reporter cells, we found evidence for fold-change detection. Although the level of nuclear Smad3 varied across cells, the fold change in the level of nuclear Smad3 was a more precise outcome of ligand stimulation...
March 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28320106/ctrp3-attenuates-hepatic-stellate-cell-activation-through-transforming-growth-factor-%C3%AE-smad-signaling-pathway
#6
Chuantao Cheng, Shuo Yu, Ran Kong, Qinggong Yuan, Yuefeng Ma, Wenbin Yang, Gang Cao, Liyi Xie
Activation of hepatic stellate cells (HSCs) plays a pivotal role in the development of liver fibrosis. C1q/tumor necrosis factor-related protein 3 (CTRP3), a member of CTRPs, was involved in fibrosis. However, little is known about the role of CTRP3 in liver fibrosis. This study aimed to determine its role in liver fibrosis and explore the possible mechanism. Our results demonstrated that CTRP3 was lowly expressed in liver fibrosis tissues and activated HSCs. Overexpression of CTRP3 inhibited the proliferation and migration of HSCs, as well as suppressed the expression of extracellular matrix (ECM) in transforming growth factor-β1 (TGF-β1)-stimulated HSC-T6 cells...
March 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28318631/the-antihelmenthic-phosphate-niclosamide-impedes-renal-fibrosis-by-inhibiting-homeodomain-interacting-protein-kinase-2-expression
#7
Xiaoyan Chang, Xin Zhen, Jixing Liu, Xiaomei Ren, Zheng Hu, Zhanmei Zhou, Fengxin Zhu, Ke Ding, Jing Nie
Renal fibrosis is the final common pathway of all varieties of progressive chronic kidney disease. However, there are no effective therapies to prevent or slow the progression of renal fibrosis. Niclosamide is a US Food and Drug Administration-approved oral antihelminthic drug used for treating most tapeworm infections. Here, we demonstrated that phosphate niclosamide, the water-soluble form of niclosamide, significantly reduced proteinuria, glomerulosclrotic lesions, and interstitial fibrosis in a murine model of adriamycin nephropathy...
March 16, 2017: Kidney International
https://www.readbyqxmd.com/read/28303407/evodiamine-attenuates-tgf-%C3%AE-1-induced-fibroblast-activation-and-endothelial-to-mesenchymal-transition
#8
Qing-Qing Wu, Yang Xiao, Xiao-Han Jiang, Yuan Yuan, Zheng Yang, Wei Chang, Zhou-Yan Bian, Qi-Zhu Tang
The aim of this study is to investigate the effect of evodiamine on fibroblast activation in cardiac fibroblasts and endothelial to mesenchymal transition (EndMT) in human umbilical vein endothelial cells (HUVECs). Neonatal rat cardiac fibroblasts were stimulated with transforming growth factor beta 1 (TGF-β1) to induce fibroblast activation. After co-cultured with evodiamine (5, 10 μM), the proliferation and pro-fibrotic proteins expression of cardiac fibroblasts were evaluated. HUVECs were also stimulated with TGF-β1 to induce EndMT and treated with evodiamine (5, 10 μM) at the same time...
March 16, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28300638/astaxanthin-attenuated-pressure-overload-induced-cardiac-dysfunction-and-myocardial-fibrosis-partially-by-activating-sirt1
#9
Jun Zhang, Quan-Zhen Wang, Shao-Hua Zhao, Xiang Ji, Jie Qiu, Jian Wang, Yi Zhou, Qian Cai, Jie Zhang, Hai-Qing Gao
BACKGROUND: Myocardial fibrosis contributes to cardiac dysfunction. Astaxanthin (AST), a member of the carotenoid family, is a well-known antioxidant, but its effect on and underlying mechanisms in myocardial fibrosis are poorly understood. METHODS: In vivo, myocardial fibrosis and cardiac dysfunction were induced using transverse aortic constriction (TAC). AST was administered to mice for 12weeks post-surgery. In vitro, transforming growth factor β1 (TGF-β1) was used to stimulate human cardiac fibroblasts (HCFs)...
March 12, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28300338/chinese-1-strain-of-toxoplasma-gondii-excreted-secreted-antigens-negatively-modulate-foxp3-via-inhibition-of-the-tgf%C3%A3-rii-smad2-smad3-smad4-pathway
#10
Jinling Chen, Caiqun Huang, Dandan Zhu, Pei Shen, Yinong Duan, Jianxin Wang, Chunzhao Yang, Liting Wu
Toxoplasma gondii is an opportunistic intracellular parasite and is considered an important aetiological factor in the process of abortion, especially as occurs in early gestation. Chinese 1 strain of T. gondii is a dominant genotype prevalent in China. Although it is known that early foetal resorption triggered by RH strain of T. gondii is attributable to immune mechanisms rather than its direct effect in uterus, the underlying mechanism of the abortion caused by Chinese 1 strain remains unclear. This study was designed to investigate the effect of excreted-secreted antigens (ESA) of Chinese 1 strain of T...
March 16, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28298524/novel-noncatalytic-substrate-selective-p38%C3%AE-specific-mapk-inhibitors-with-endothelial-stabilizing-and-anti-inflammatory-activity
#11
Nirav G Shah, Mohan E Tulapurkar, Aparna Ramarathnam, Amanda Brophy, Ramon Martinez, Kellie Hom, Theresa Hodges, Ramin Samadani, Ishwar S Singh, Alexander D MacKerell, Paul Shapiro, Jeffrey D Hasday
The p38 MAPK family is composed of four kinases of which p38α/MAPK14 is the major proinflammatory member. These kinases contribute to many inflammatory diseases, but the currently available p38 catalytic inhibitors (e.g., SB203580) are poorly effective and cause toxicity. We reasoned that the failure of catalytic p38 inhibitors may derive from their activity against noninflammatory p38 isoforms (e.g., p38β/MAPK11) and loss of all p38α-dependent responses, including anti-inflammatory, counterregulatory responses via mitogen- and stress-activated kinase (MSK) 1/2 and Smad3...
March 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28290051/construction-of-a-comprehensive-protein-protein-interaction-map-for-vitiligo-disease-to-identify-key-regulatory-elements-a-systemic-approach
#12
Anvita Gupta Malhotra, Mohit Jha, Sudha Singh, Khushhali M Pandey
Vitiligo is an idiopathic disorder characterized by depigmented patches on the skin due to progressive loss of melanocytes. Several genetic, immunological, and pathophysiological investigations have established vitiligo as a polygenetic disorder with multifactorial etiology. However, no definite model explaining the interplay between these causative factors has been established hitherto. Therefore, we studied the disorder at the system level to identify the key proteins involved by exploring their molecular connectivity in terms of topological parameters...
March 13, 2017: Interdisciplinary Sciences, Computational Life Sciences
https://www.readbyqxmd.com/read/28288584/adipose-tissue-fibrosis-in-human-cancer-cachexia-the-role-of-tgf%C3%AE-pathway
#13
Michele Joana Alves, Raquel Galvão Figuerêdo, Flavia Figueiredo Azevedo, Diego Alexandre Cavallaro, Nelson Inácio Pinto Neto, Joanna Darck Carola Lima, Emidio Matos-Neto, Katrin Radloff, Daniela Mendes Riccardi, Rodolfo Gonzalez Camargo, Paulo Sérgio Martins De Alcântara, José Pinhata Otoch, Miguel Luiz Batista Junior, Marília Seelaender
BACKGROUND: Cancer cachexia is a multifactorial syndrome that dramatically decreases survival. Loss of white adipose tissue (WAT) is one of the key characteristics of cachexia. WAT wasting is paralleled by microarchitectural remodeling in cachectic cancer patients. Fibrosis results from uncontrolled ECM synthesis, a process in which, transforming growth factor-beta (TGFβ) plays a pivotal role. So far, the mechanisms involved in adipose tissue (AT) re-arrangement, and the role of TGFβ in inducing AT remodeling in weight-losing cancer patients are poorly understood...
March 14, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28288136/oncostatin-m-promotes-cancer-cell-plasticity-through-cooperative-stat3-smad3-signaling
#14
D J Junk, B L Bryson, J M Smigiel, N Parameswaran, C A Bartel, M W Jackson
Increasing evidence supports the idea that cancer cell plasticity promotes metastasis and tumor recurrence, resulting in patient mortality. While it is clear that the tumor microenvironment (TME) contributes to cancer cell plasticity, the specific TME factors most actively controlling plasticity remain largely unknown. Here, we performed a screen to identify TME cytokines and growth factors that promote epithelial-mesenchymal plasticity, and acquisition of cancer stem cell (CSC) properties. Of 28 TME cytokines and growth factors tested, we identified Oncostatin M (OSM) as the most potent inducer of mesenchymal/CSC properties...
March 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28286188/endovascular-repair-of-internal-mammary-artery-aneurysms-in-two-sisters-with-smad3-mutation
#15
Daiva Nevidomskyte, Sherene Shalhub, Gabriel S Aldea, Peter H Byers, Ulrike Schwarze, Mitzi L Murray, Benjamin Starnes
True aneurysms of the internal mammary artery are rare and have been described in association with vasculitis or connective tissue disorders. Herein we describe two cases of familial internal mammary artery aneurysms in two sisters with SMAD3 mutation. The older sister presented at the age of 54 with an incidental diagnosis of a multilobed right internal mammary artery aneurysm (IMA) and the younger sister presented several years earlier with a ruptured left IMA aneurysm at the age of 49. Both sisters had Debakey type I aortic dissections prior to the IMA aneurysm presentation...
March 7, 2017: Annals of Vascular Surgery
https://www.readbyqxmd.com/read/28273365/metformin-attenuates-renal-fibrosis-in-both-ampk%C3%AE-2-dependent-and-independent-manners
#16
Yenan Feng, Shuaixing Wang, Youyi Zhang, Han Xiao
Metformin is a well-known AMP-activated protein kinase (AMPK) activator, and it has been shown to inhibit organ fibrosis. Whether AMPKα2 mediates metformin protection against renal fibrosis remains unknown. Here, we aimed to investigate the role of the AMPKα2 isoform in mediating the inhibitory effect of metformin on renal fibrosis. Unilateral ureteral obstruction (UUO) was used to induce renal fibrosis in wild-type (WT) and AMPKα2 knockout (AMPKα2(-/-) ) mice. Metformin treatment was initiated 3 days before UUO and was continued until 7 days after UUO...
March 8, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28267785/smad3-dependent-ccn2-mediates-fibronectin-expression-in-human-skin-dermal-fibroblasts
#17
Trupta Purohit, Zhaoping Qin, Chunji Quan, Zhenhua Lin, Taihao Quan
The potential involvement of connective tissue growth factor (CCN2/CTGF) in extracellular matrix (ECM) production is recognized. However, the role CCN2 in fibronectin (FN) gene expression has remained incompletely understood and even controversial. Here we report that CCN2 is absolutely necessary for FN expression in primary human skin dermal fibroblasts, the major cells responsible for ECM production in skin. Gain- and loss-of-function approaches demonstrate that CCN2 is an essential component of FN expression in both basal and stimulation by TGF-β signaling, the major regulator of FN expression...
2017: PloS One
https://www.readbyqxmd.com/read/28263294/increased-expression-of-latent-tgf-%C3%AE-binding-protein-4-affects-the-fibrotic-process-in-scleroderma-by-tgf-%C3%AE-smad-signaling
#18
Jiaying Lu, Qingmei Liu, Lei Wang, Wenzhen Tu, Haiyan Chu, Weifeng Ding, Shuai Jiang, Yanyun Ma, Xiangguang Shi, Weilin Pu, Xiaodong Zhou, Li Jin, Jiucun Wang, Wenyu Wu
Scleroderma is a fibrosis-related disorder characterized by cutaneous and internal organ fibrosis, and excessive collagen deposition in extracellular matrix (ECM) is a major cause of fibrosis. Transforming growth factor-β (TGF-β)/SMAD signaling has a central role in the pathogenesis of fibrosis by inducing abnormal collagen accumulation in ECM, and latent TGF-β-binding protein 4 (LTBP-4) affects the secretion of latent TGF-β to ECM. A previous study indicated that bleomycin (BLM) treatment increased LTBP-4 expression in lung fibroblasts of Thy-1 knockout mice with lung fibrosis, and LTBP-4 further promoted TGF-β bioavailability as well as SMAD3 phosphorylation...
March 6, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28262747/smad3-promotes-cancer-progression-by-inhibiting-e4bp4-mediated-nk-cell-development
#19
Patrick Ming-Kuen Tang, Shuang Zhou, Xiao-Ming Meng, Qing-Ming Wang, Chun-Jie Li, Guang-Yu Lian, Xiao-Ru Huang, Yong-Jiang Tang, Xin-Yuan Guan, Bryan Ping-Yen Yan, Ka-Fai To, Hui-Yao Lan
TGF-β is known to influence tumour progression. Here we report an additional role of Smad3 in the tumour microenvironment regulating cancer progression. Deletion or inhibition of Smad3 in the tumour microenvironment suppresses tumour growth, invasion and metastasis in two syngeneic mouse tumour models. Smad3(-/-) bone marrow gives rise to an expanded NK cell population with enhanced tumour-suppressive activities in vivo, and promotes differentiation of NK cells ex vivo. We identify E4BP4/NFIL3 as a direct Smad3 target gene critical for NK cell differentiation...
March 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28262301/effects-of-alcohol-on-postoperative-adhesion-formation-in-ischemic-myocardium-and-pericardium
#20
Nassrene Y Elmadhun, Ashraf A Sabe, Antonio D Lassaletta, Rahul S Dalal, Frank W Sellke
BACKGROUND: Postoperative formation of adhesions increases risk of complications during cardiac reoperations. We previously demonstrated that swine supplemented with vodka had a significant reduction in adhesions at sternotomy after previous thoracotomy. This follow-up study was conducted to determine reproducibility and the mechanism for adhesion reduction in swine supplemented with ethanol. METHODS: An ameroid constrictor was placed in the left circumflex in 14 male Yorkshire swine to induce chronic myocardial ischemia through left minithoracotomy...
March 2, 2017: Annals of Thoracic Surgery
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