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https://www.readbyqxmd.com/read/29753718/early-tgf-%C3%AE-inhibition-in-mice-reduces-the-incidence-of-breast-cancer-induced-bone-disease-in-a-myeloid-dependent-manner
#1
Denise Buenrostro, Kristin A Kwakwa, Nicole E Putnam, Alyssa R Merkel, Joshua R Johnson, James E Cassat, Julie A Sterling
The tumor-cell microenvironment is recognized as a dynamic place where critical cell interactions occur and play an important role in altering tumorigenesis. While many studies have investigated the effects of cellular cross-talk within distinct tumor microenvironments, these interactions have yet to be fully examined in bone. It is well-established that many common cancers metastasize to bone, resulting in the development of tumor-induced bone disease (TIBD), a multi-facetted illness that is driven by complex cell interactions within the bone marrow...
May 10, 2018: Bone
https://www.readbyqxmd.com/read/29748374/the-microrna-371-373-cluster-represses-colon-cancer-initiation-and-metastatic-colonization-by-inhibiting-the-tgfbr2-id1-signaling-axis
#2
Pit Ullmann, Fabien Rodriguez, Martine Schmitz, Steffen K Meurer, Komal Qureshi-Baig, Paul Felten, Aurélien Ginolhac, Laurent Antunes, Sonia Frasquilho, Nikolaus Zügel, Ralf Weiskirchen, Serge Haan, Elisabeth Letellier
The vast majority of colorectal cancer (CRC)-related deaths can be attributed to metastatic spreading of the disease. Therefore, deciphering molecular mechanisms of metastatic dissemination is a key prerequisite to improve future treatment options. With this aim, we took advantage of different CRC cell lines and recently established primary cultures enriched in colon cancer stem cells (CSCs) - also known as tumor-initiating cells (TICs) - to identify genes and microRNAs (miRNAs) with regulatory functions in CRC progression...
May 10, 2018: Cancer Research
https://www.readbyqxmd.com/read/29739329/thrombin-and-factor-xa-link-the-coagulation-system-with-liver-fibrosis
#3
Ameet Dhar, Fouzia Sadiq, Quentin M Anstee, Adam P Levene, Robert D Goldin, Mark R Thursz
BACKGROUND: Thrombin activates hepatic stellate cells via protease-activated receptor-1. The role of Factor Xa (FXa) in hepatic fibrosis has not been elucidated. We aimed to evaluate the impact of FXa and thrombin in vitro on stellate cells and their respective inhibition in vivo using a rodent model of hepatic fibrosis. METHODS: HSC-LX2 cells were incubated with FXa and/or thrombin in cell culture, stained for αSMA and relative gene expression and gel contraction calculated...
May 8, 2018: BMC Gastroenterology
https://www.readbyqxmd.com/read/29726981/dickkopf-3-in-aberrant-endothelial-secretome-triggers-renal-fibroblast-activation-and-endothelial-mesenchymal-transition
#4
Mark Lipphardt, Hassan Dihazi, Noo Li Jeon, Sina Dadafarin, Brian B Ratliff, David W Rowe, Gerhard A Müller, Michael S Goligorsky
Background: Our laboratory has previously demonstrated that Sirt1endo-/- mice show endothelial dysfunction and exaggerated renal fibrosis, whereas mice with silenced endothelial transforming growth factor beta (TGF-β) signaling are resistant to fibrogenic signals. Considering the fact that the only difference between these mutant mice is confined to the vascular endothelium, this indicates that secreted substances contribute to these contrasting responses. Methods: We performed an unbiased proteomic analysis of the secretome of renal microvascular endothelial cells (RMVECs) isolated from these two mutants...
May 3, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29723998/the-ebv-encoded-oncoprotein-lmp1-induces-an-epithelial-to-mesenchymal-transition-emt-via-its-ctar1-domain-through-integrin-mediated-erk-mapk-signalling
#5
Mhairi A Morris, Louise Laverick, Wenbin Wei, Alexandra M Davis, Samantha O'Neill, Liam Wood, Jack Wright, Christopher W Dawson, Lawrence S Young
The Epstein⁻Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) oncogene can induce profound effects on epithelial growth and differentiation including many of the features of the epithelial-to-mesenchymal transition (EMT). To better characterise these effects, we used the well-defined Madin Darby Canine Kidney (MDCK) epithelial cell model and found that LMP1 expression in these cells induces EMT as defined by characteristic morphological changes accompanied by loss of E-cadherin, desmosomal cadherin and tight junction protein expression...
May 1, 2018: Cancers
https://www.readbyqxmd.com/read/29723859/upregulation-of-nox2-and-nox4-mediated-by-tgf-%C3%AE-signaling-pathway-exacerbates-cerebral-ischemia-reperfusion-oxidative-stress-injury
#6
Zheng Lou, Ai-Ping Wang, Xiao-Ming Duan, Guo-Huang Hu, Gui-Lin Song, Mei-Ling Zuo, Zhong-Bao Yang
BACKGROUND/AIMS: Ischemic stroke is still one of the leading debilitating diseases with high morbidity and mortality. NADPH oxidase (NOX)-derived reactive oxygen species (ROS) play an important role in cerebral ischemia/reperfusion (I/R) injury. However, the mechanism underlying the regulation of ROS generation is still not fully elucidated. This study aims to explore the role of transforming growth beta (TGF-β) signals in ROS generation. METHODS: Sprague-Dawley rats were subjected to I/R injury, and PC-12 cells were challenged by hypoxia/reoxygenation (H/R) and/or treated with activin receptor-like kinase (ALK5) inhibitor Sb505124 or siRNA against ALK5...
2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29710775/novel-ex-vivo-human-osteochondral-explant-model-of-knee-and-spine-osteoarthritis-enables-assessment-of-inflammatory-and-drug-treatment-responses
#7
Jeroen Geurts, Doria Jurić, Miriam Müller, Stefan Schären, Cordula Netzer
Osteoarthritis of the knee and spine is highly prevalent in modern society, yet a disease-modifying pharmacological treatment remains an unmet clinical need. A major challenge for drug development includes selection of appropriate preclinical models that accurately reflect clinical phenotypes of human disease. The aim of this study was to establish an ex vivo explant model of human knee and spine osteoarthritis that enables assessment of osteochondral tissue responses to inflammation and drug treatment. Equal-sized osteochondral fragments from knee and facet joints (both n = 6) were subjected to explant culture for 7 days in the presence of a toll-like receptor 4 (TLR4) agonist and an inhibitor of transforming growth factor-beta (TGF-β) receptor type I signaling...
April 28, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29701666/tgf-%C3%AE-and-the-tissue-microenvironment-relevance-in-fibrosis-and-cancer
#8
REVIEW
Laia Caja, Francesco Dituri, Serena Mancarella, Daniel Caballero-Diaz, Aristidis Moustakas, Gianluigi Giannelli, Isabel Fabregat
Transforming growth factor-β (TGF-β) is a cytokine essential for the induction of the fibrotic response and for the activation of the cancer stroma. Strong evidence suggests that a strong cross-talk exists among TGF-β and the tissue extracellular matrix components. TGF-β is stored in the matrix as part of a large latent complex bound to the latent TGF-β binding protein (LTBP) and matrix binding of latent TGF-β complexes, which is required for an adequate TGF-β function...
April 26, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29695674/induction-of-myosin-light-chain-kinase-and-cpi-17-by-tgf-%C3%AE-accelerates-contractile-activity-in-intestinal-epithelial-cells
#9
Md Shafiqul Islam, Noriyuki Kaji, Shoma Mikawa, Qunhui Yang, Moriaki Kusabe, Masatoshi Hori, Hiroshi Ozaki
Epithelial-mesenchymal transition (EMT) is an orchestral and functional change in epithelial cells. Many signaling pathways are involved in EMT, and transforming growth factor-beta (TGF-β) is considered to be one of the most important factors in induction of EMT. In this study, we treated the rat intestinal epithelial cell line (IEC-6) with TGF-β1 as a signaling stimulant. Gross analysis of IEC-6 cells showed typical characteristics of epithelial cells such as cuboidal morphology and cell-cell contact, whereas treatment with TGF-β1 (10 ng·ml-1 ) for 7 days produced robust, spindle-shaped morphology...
April 24, 2018: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/29693588/relative-contribution-of-cellular-complement-inhibitors-cd59-cd46-and-cd55-to-parainfluenza-virus-5-inhibition-of-complement-mediated-neutralization
#10
Yujia Li, Griffith D Parks
The complement system is a part of the innate immune system that viruses need to face during infections. Many viruses incorporate cellular regulators of complement activation (RCA) to block complement pathways and our prior work has shown that Parainfluenza virus 5 (PIV5) incorporates CD55 and CD46 to delay complement-mediated neutralization. In this paper, we tested the role of a third individual RCA inhibitor CD59 in PIV5 interactions with complement pathways. Using a cell line engineered to express CD59, we show that small levels of functional CD59 are associated with progeny PIV5, which is capable of blocking assembly of the C5b-C9 membrane attack complex (MAC)...
April 25, 2018: Viruses
https://www.readbyqxmd.com/read/29671258/atrial-overexpression-of-microrna-27b-attenuates-angiotensin-ii-induced-atrial-fibrosis-and-fibrillation-by-targeting-alk5
#11
Yanshan Wang, Heng Cai, Hongmei Li, Zhisheng Gao, Kunqing Song
Atrial fibrosis influences atrial fibrillation (AF) development by transforming growth factor beta 1 (TGF-β1)/Smad pathway. Although microRNAs are implicated in the pathogenesis of various diseases, information regarding the functional role of microRNAs in atrial dysfunction is limited. In the present study, we found that microRNA-27b (miR-27b) was the dominant member of miR-27 family expressed in left atrium. Moreover, the expression of miR-27b was significantly reduced after angiotensin II (AngII) infusion...
April 18, 2018: Human Cell
https://www.readbyqxmd.com/read/29659051/psa-alpha-2-macroglobulin-complex-is-enzymatically-active-in-the-serum-of-patients-with-advanced-prostate-cancer-and-can-degrade-circulating-peptide-hormones
#12
Maya B Kostova, William Nathaniel Brennen, David Lopez, Lizamma Anthony, Hao Wang, Elizabeth Platz, Samuel R Denmeade
BACKGROUND: Prostate cancer cells produce high levels of the serine protease Prostate-Specific Antigen (PSA). PSA is enzymatically active in the tumor microenvironment but is presumed to be enzymatically inactive in the blood due to complex formation with serum protease inhibitors α-1-antichymotrypsin and α-2-macroglobulin (A2M). PSA-A2M complexes cannot be measured by standard ELISA assays and are also rapidly cleared from the circulation. Thus the exact magnitude of PSA production by prostate cancer cells is not easily measured...
April 16, 2018: Prostate
https://www.readbyqxmd.com/read/29623491/the-complex-alteration-in-the-network-of-il-17-type-cytokines-in-patients-with-hereditary-angioedema
#13
Francesco Arcoleo, Mariangela Lo Pizzo, Gabriella Misiano, Salvatore Milano, Giuseppina Colonna Romano, Vito Muggeo, Enrico Cillari
Hereditary angioedema (HAE) is a rare autosomic-dominant disorder characterized by a deficiency of C1 esterase inhibitor which causes episodic swellings of subcutaneous tissues, bowel walls and upper airways that are disabling and potentially life-threatening. We evaluated n = 17 patients with confirmed HAE diagnosis during attack and remission state and n = 19 healthy subjects. The samples were tested for a panel of IL (Interleukin)-17-type cytokines (IL-1β, IL-6, IL-10, granulocyte-macrophage colony stimulating factor (GM-CSF), IL-17, IL-21, IL-22, IL-23) and transforming growth factor-beta (TGF-β) subtypes...
April 6, 2018: Clinical and Experimental Medicine
https://www.readbyqxmd.com/read/29622010/mechanical-barriers-and-transforming-growth-factor-beta-inhibitor-on-epidural-fibrosis-in-a-rabbit-laminectomy-model
#14
Juan N Albiñana-Cunningham, Purificación Ripalda-Cemboráin, Tania Labiano, José I Echeveste, Froilán Granero-Moltó, Matías Alfonso-Olmos
BACKGROUND: TGF-β has been described as a mediator of fibrosis and scarring. Several studies achieved reduction in experimental scarring through the inhibition of TGF-β. Fibroblasts have been defined as the cell population originating fibrosis, blocking fibroblast invasion may impair epidural fibrosis appearance. For this purpose, biocompatible materials used as mechanical barriers and a TGF-β inhibitor peptide were evaluated in the reduction of epidural fibrosis. METHODS: A L6 laminectomy was performed in 40 New Zealand white rabbits...
April 5, 2018: Journal of Orthopaedic Surgery and Research
https://www.readbyqxmd.com/read/29599317/transforming-growth-factor-beta-produced-by-non-small-cell-lung-cancer-cells-contributes-to-lung-fibroblast-contractile-phenotype
#15
Nobuhiro Kanaji, Masanao Yokohira, Naoki Watanabe, Norimitsu Kadowaki, Shuji Bandoh
BACKGROUND/AIM: Fibroblasts can alter the extracellular matrix (ECM), contributing to cancer progression by providing a scaffold for cancer cells. The influence of lung cancer cells (LCCs) on lung fibroblast-mediated ECM alteration is not well understood. MATERIALS AND METHODS: After incubation in serum-free medium, LCC- or fibroblast-conditioned media were collected. The ECM alteration was assessed by collagen gel contraction assay. RESULTS: Both LCC-conditioned medium and exogenous transforming growth factor (TGF)-β1 increased collagen gel contraction by lung fibroblasts...
April 2018: Anticancer Research
https://www.readbyqxmd.com/read/29578200/epigallocatechin-gallate-curcumin-prevent-transforming-growth-factor-beta-1-induced-epithelial-to-mesenchymal-transition-in-arpe-19-cells
#16
Sivasankar Shanmuganathan, Venil N Sumantran, Narayanasamy Angayarkanni
Background & objectives: Proliferative vitreoretinopathy (PVR) is characterized by the presence of epiretinal membrane (ERM), which exerts traction and detaches the retina. Epithelial to mesenchymal transition (EMT) of the retinal pigment epithelial (RPE) cells underlies ERM formation. Adjuvant therapies aimed at preventing recurrence of PVR after surgery mostly failed in clinical trials. This study was aimed to evaluate the anti-EMT properties of bio-active compounds epigallocatechin gallate (EGCG), curcumin and lycopene as inhibitors of EMT induced by transforming growth factor beta 1 (TGF-β1) in cultured ARPE-19 cells...
November 2017: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/29577907/possible-role-of-ginsenoside-rb1-in-skin-wound-healing-via-regulating-senescent-skin-dermal-fibroblast
#17
Jingang Hou, Sunchang Kim
Cellular senescence suppresses cancer by inducing irreversible cell growth arrest. Nevertheless, senescent cells is proposed as causal link with aging and aging-related pathologies. The physiological beneficial functions of senescent cells are still of paucity. Here we show that senescent human dermal fibroblast accelerates keratinocytes scratch wound healing and stimulates differentiation of fibroblast. Using oxidative stress (100 μM H2 O2 exposure for 1 h) induction, we successfully triggered fibroblast senescence and developed senescence associated secretory phenotype (SASP)...
March 22, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29560281/regulation-of-transforming-growth-factor-is-involved-in-the-efficacy-of-combined-5-fluorouracil-and-interferon-alpha-2b-therapy-of-advanced-hepatocellular-carcinoma
#18
Youhei Okada, Ting Wang, Kazuhiro Kasai, Kazuyuki Suzuki, Yasuhiro Takikawa
Transforming growth factor-beta (TGF-β) is critical in cancer cell invasion and metastasis. The effects of a treatment that targets TGF-β using the combination of interferon alpha (IFNα)-2b and 5-fluorouracil (5-FU) are unknown. Here, we show that the serum levels of TGF-β1 prior to the therapy correlate with increased maximum tumor diameter, which is significantly ( p  < 0.01) decreased after the combination therapy. 5-FU increased both the expression and secretion levels of TGF-β1 in hepatoma cells, but not in normal hepatocytes...
2018: Cell Death Discovery
https://www.readbyqxmd.com/read/29487140/bone-morphogenetic-protein-9-reduces-cardiac-fibrosis-and-improves-cardiac-function-in-heart-failure
#19
Kevin J Morine, Xiaoying Qiao, Sam York, Peter S Natov, Vikram Paruchuri, Yali Zhang, Mark J Aronovitz, Richard H Karas, Navin K Kapur
Background -Heart failure is a growing cause of morbidity and mortality worldwide. Transforming growth factor beta (TGF-β1) promotes cardiac fibrosis, but also activates counter-regulatory pathways that serve to regulate TGF-β1 activity in heart failure. Bone morphogenetic protein 9 (BMP9) is a member of the TGFβ family of cytokines and signals via the downstream effector protein Smad1. Endoglin is a TGFβ co-receptor that promotes TGF-β1 signaling via Smad3 and binds BMP9 with high affinity. We hypothesized that BMP9 limits cardiac fibrosis by activating Smad1 and attenuating Smad3 and further that neutralizing endoglin activity promotes BMP9 activity...
February 27, 2018: Circulation
https://www.readbyqxmd.com/read/29467938/smad4-independent-activation-of-tgf-%C3%AE-signaling-by-muc1-in-a-human-pancreatic-cancer-cell-line
#20
Priyanka Grover, Sritama Nath, Monica D Nye, Ru Zhou, Mohammad Ahmad, Pinku Mukherjee
Pancreatic Ductal Adenocarcinoma (PDA) has a mortality rate that nearly matches its incidence rate. Transforming Growth Factor Beta (TGF-β) is a cytokine with a dual role in tumor development switching from a tumor suppressor to a tumor promoter. There is limited knowledge of how TGF-β function switches during tumorigenesis. Mucin 1 (MUC1) is an aberrantly glycosylated, membrane-bound, glycoprotein that is overexpressed in >80% of PDA cases and is associated with poor prognosis. In PDA, MUC1 promotes tumor progression and metastasis via signaling through its cytoplasmic tail (MUC1-CT) and interacting with other oncogenic signaling molecules...
January 23, 2018: Oncotarget
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