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https://www.readbyqxmd.com/read/28829835/exogenous-growth-factors-bfgf-egf-and-hgf-do-not-influence-viability-and-phenotype-of-v600ebraf-melanoma-cells-and-their-response-to-vemurafenib-and-trametinib-in-vitro
#1
Izabela Zalesna, Marta Osrodek, Mariusz L Hartman, Michal Rozanski, Malgorzata Sztiller-Sikorska, Karolina Niewinna, Dariusz Nejc, Malgorzata Czyz
It has been shown that the response of V600EBRAF melanoma cells to targeted therapeutics is affected by growth factors. We have investigated the influence of three different growth factors, bFGF, EGF and HGF used either alone or in combination, on the response of V600EBRAF melanoma cell populations established from surgical specimens to vemurafenib and trametinib, targeting V600EBRAF and MEK1/2, respectively. We report that proliferation and phenotype of V600EBRAF melanoma cell populations were not detectably influenced by exogenous growth factors...
2017: PloS One
https://www.readbyqxmd.com/read/28822004/in-vitro-validation-of-the-hippo-pathway-as-a-pharmacological-target-for-canine-mammary-gland-tumors
#2
Samantha Guillemette, Charlène Rico, Philippe Godin, Derek Boerboom, Marilène Paquet
Canine mammary tumors (CMTs) are the most common neoplasms in intact female dogs. Some clinical and molecular similarities between certain CMT subtypes and breast cancer make them a potential model for the study of the human disease. As misregulated Hippo signaling is thought to play an important role in breast cancer development and also occurs in CMTs, we sought to determine if Hippo represents a valid pharmacological target for the treatment of CMTs. Six CMT cell lines were assessed for their expression of the Hippo pathway effectors YAP and TAZ and for their sensitivity to verteporfin, an inhibitor of YAP-mediated transcriptional coactivation...
August 18, 2017: Journal of Mammary Gland Biology and Neoplasia
https://www.readbyqxmd.com/read/28819999/high-glucose-induces-hgf-independent-activation-of-met-receptor-in-human-renal-tubular-epithelium
#3
Lucia Mesarosova, Peter Ochodnicky, Jaklien C Leemans, Sandrine Florquin, Peter Krenek, Jan Klimas
CONTEXT: The role of hepatocyte growth factor (HGF) in diabetic kidney damage remains controversial. OBJECTIVE: To test the hypothesis that high glucose levels activate pathways related to HGF and its receptor Met and that this could participate in glucose-induced renal cell damage. MATERIALS AND METHODS: HK2 cells, a human proximal tubule epithelial cell line, were stimulated with high glucose for 48 hours. Levels of pMet/Met, pEGFR/EGFR, pSTAT3/STAT3, pAkt/Akt and pERK1/2/ERK1/2 were studied by immunoblotting...
August 18, 2017: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/28819120/dual-delivery-of-fgf-2-ctgf-from-silk-fibroin-plcl-peo-coaxial-fibers-enhances-msc-proliferation-and-fibrogenesis
#4
Ruodan Xu, Huiling Zhao, Hanif Muhammad, Mingdong Dong, Flemming Besenbacher, Menglin Chen
The success of mesenchymal stem cell transplantation is highly dependent on their survival and controlled fate regulation. This study demonstrates that dual-delivery of connective tissue growth factor (CTGF) and fibroblast growth factor 2 (FGF-2) from a core-shell fiber of Silk Fibroin/poly(L-lactic acid-co-ε-caprolactone)-polyethylene oxide (SF/PLCL-PEO) enhanced fibrogenic lineage differentiation of MSCs. The core-shell structure was confirmed by transmission electron microscopy (TEM), fluorescence microscopy and attenuated total reflection (ATR) Fourier transform infrared (FTIR) spectroscopy...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28816418/hypoxia-induced-microrna-26b-inhibition-contributes-to-hypoxic-pulmonary-hypertension-via-ctgf
#5
Sijing Zhou, Li Sun, Chao Cao, Peipei Wu, Min Li, Gengyun Sun, Guanghe Fei, Xing Ding, Ran Wang
The objective of this study was to explore the role of miRNAs in the control of HPH as well as molecular mechanism underlying. Computational analysis and luciferase assay were carried out to search the target gene of miR-26b. Luciferase assay, RT-PCR and western-blot analysis was performed to test interaction among hypoxia, miR-26b, SRF and CTGF. MiR-26b was significantly downregulated; meanwhile, CTGF and SRF were significantly upregulated in HPH rat model. Using computational analysis, CTGF was found to be a virtual target gene of miR-26b, and only cell transfected with vectors containing wild-type CTGF 3'UTR and miR-26b showed a lower luciferase activity than scramble control...
August 17, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28815607/a-3d-tri-culture-system-reveals-that-activin-receptor-like-kinase-5-and-connective-tissue-growth-factor-drive-human-glomerulosclerosis
#6
John P Waters, Yvonne C Richards, Jeremy N Skepper, Mark Southwood, Paul D Upton, Nicholas W Morrell, Jordan S Pober, John R Bradley
Glomerular scarring, known as glomerulosclerosis, occurs in many chronic kidney diseases and involves interaction between glomerular endothelial cells (GEC), podocytes and mesangial cells (MCs), leading to signals that promote extracellular matrix deposition and endothelial cell dysfunction and loss. We describe a 3D tri-culture system to model human glomerulosclerosis. In 3D monoculture, each cell type alters its phenotype in response to TGFβ, which has been implicated as an important mediator of glomerulosclerosis...
August 16, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28807595/sphingosine-kinase-2-deficiency-ameliorates-kidney-fibrosis-by-up-regulating-smad7-in-a-mouse-model-of-unilateral-ureteral-obstruction
#7
Stephanie Schwalm, Sandra Beyer, Helena Frey, Riad Haceni, Georgios Grammatikos, Dominique Thomas, Gerd Geisslinger, Liliana Schaefer, Andrea Huwiler, Josef Pfeilschifter
Kidney fibrosis is a hallmark of chronic kidney disease and leads to extracellular matrix accumulation, organ scarring, and loss of kidney function. In this study, we investigated the role of sphingosine kinase-2 (SPHK2) on the progression of tubular fibrosis by utilizing a mouse unilateral ureteral obstruction (UUO) model. We found that SPHK2 protein and activity are up-regulated in fibrotic renal tissue. Functionally, Sphk2 deficient (Sphk2(-/-)) mice showed an attenuated fibrotic response to UUO compared to wild-type mice as demonstrated by reduced collagen abundance and decreased expression of fibronectin-1, collagen I, α-smooth muscle actin, connective tissue growth factor (CTGF), and plasminogen activator inhibitor (PAI-1)...
August 11, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28798388/angiotensin-ii-induces-connective-tissue-growth-factor-expression-in-human-hepatic-stellate-cells-by-a-transforming-growth-factor-%C3%AE-independent-mechanism
#8
Ao Li, Jingyao Zhang, Xiaoxun Zhang, Jun Wang, Songsong Wang, Xiao Xiao, Rui Wang, Peng Li, Yitao Wang
Angiotensin II (Ang II) promotes hepatic fibrosis by increasing extracellular matrix (ECM) synthesis. Connective tissue growth factor (CTGF) plays a crucial role in the pathogenesis of hepatic fibrosis and emerges as downstream of the profibrogenic cytokine transforming growth factor-β (TGF-β). We aimed to investigate the molecular events that lead from the Ang II receptor to CTGF upregulation in human hepatic stellate cells, a principal fibrogenic cell type. Ang II produced an early, AT1 receptor-dependent stimulation of CTGF expression and induced a rapid activation of PKC and its downstream p38 MAPK, thereby activating a nuclear factor-κB (NF-κB) and Smad2/3 cross-talk pathway...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28790340/verteporfin-inhibits-growth-of-human-glioma-in-vitro-without-light-activation
#9
Ahmad Al-Moujahed, Katarzyna Brodowska, Tomasz P Stryjewski, Nikolaos E Efstathiou, Ioannis Vasilikos, Joanna Cichy, Joan W Miller, Evangelos Gragoudas, Demetrios G Vavvas
Verteporfin (VP), a light-activated drug used in photodynamic therapy for the treatment of choroidal neovascular membranes, has also been shown to be an effective inhibitor of malignant cells. Recently, studies have demonstrated that, even without photo-activation, VP may still inhibit certain tumor cell lines, including ovarian cancer, hepatocarcinoma and retinoblastoma, through the inhibition of the YAP-TEAD complex. In this study, we examined the effects of VP without light activation on human glioma cell lines (LN229 and SNB19)...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28789938/azilsartan-ameliorates-diabetic-cardiomyopathy-in-young-db-db-mice-through-the-modulation-of-ace-2-ang-1-7-mas-receptor-cascade
#10
Vijayakumar Sukumaran, Hirotsugu Tsuchimochi, Eisuke Tatsumi, Mikiyasu Shirai, James T Pearson
Hyperglycemia up-regulates intracellular angiotensin II (ANG-II) production in cardiac myocytes. This study investigated the hemodynamic and metabolic effects of azilsartan (AZL) treatment in a mouse model of diabetic cardiomyopathy and whether the cardioprotective effects of AZL are mediated by the angiotensin converting enzyme (ACE)-2/ANG 1-7/Mas receptor (R) cascade. Control db/+ and db/db mice (n=5 per group) were treated with vehicle or AZL (1 or 3mg/kg/d oral gavage) from the age of 8 to 16weeks. Echocardiography was then performed and myocardial protein levels of ACE-2, Mas R, AT1R, AT2R, osteopontin, connective tissue growth factor (CTGF), atrial natriuretic peptide (ANP) and nitrotyrosine were measured by Western blotting...
August 5, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28782610/anti-connective-tissue-growth-factor-detects-and-reduces-plaque-inflammation-in-early-stage-carotid-atherosclerotic-lesions
#11
Yuyu Yao, Bing Li, Fu Cong, Gaojun Teng, Genshan Ma, Naifeng Liu
This study explored connective tissue growth factor (CTGF)-targeted ultrasmall superparamagnetic iron oxides (USPIOs) for noninvasive MRI of CTGF within carotid atherosclerotic lesions in apoE-deficient (apoE(-/-)) mice. Anti-CTGF polyclonal and nonspecific IgG antibodies were conjugated to polyethylene glycol-coated USPIOs, and apoE(-/-) carotid partial ligation-model mice were imaged via MRI before and after contrast administration. ApoE(-/-) mice were treated with CTGF-neutralizing antibodies for 3 weeks...
August 3, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28782260/mmp-13-deletion-decreases-profibrogenic-molecules-and-attenuates-n-nitrosodimethylamine-induced-liver-injury-and-fibrosis-in-mice
#12
Joseph George, Mikihiro Tsutsumi, Mutsumi Tsuchishima
Connective tissue growth factor (CTGF) is involved in inflammation, pathogenesis and progression of liver fibrosis. Matrix metalloproteinase-13 (MMP-13) cleaves CTGF and releases several fragments, which are more potent than the parent molecule to induce fibrosis. The current study was aimed to elucidate the significance of MMP-13 and CTGF and their downstream effects in liver injury and fibrosis. Hepatic fibrosis was induced using intraperitoneal injections of N-nitrosodimethylamine (NDMA) in doses of 10 μg/g body weight on three consecutive days of each week over a period of 4 weeks in both wild-type (WT) and MMP-13 knockout mice...
August 7, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28778086/connective-tissue-growth-factor-mediates-tgf-%C3%AE-1-induced-low-grade-serous-ovarian-tumor-cell-apoptosis
#13
Jung-Chien Cheng, Hsun-Ming Chang, Peter C K Leung
Ovarian low-grade serous carcinoma (LGSC) is a rare disease and is now considered to be a distinct entity from high-grade serous carcinoma (HGSC), which is the most common and malignant form of epithelial ovarian cancer. Connective tissue growth factor (CTGF) is a secreted matricellular protein that has been shown to modulate many biological functions by interacting with multiple molecules in the microenvironment. Increasing evidence indicates that aberrant expression of CTGF is associated with cancer development and progression...
July 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28778066/inhibition-of-lsd1-epigenetically-attenuates-oral-cancer-growth-and-metastasis
#14
Saqer F Alsaqer, Mustafa M Tashkandi, Vinay K Kartha, Ya-Ting Yang, Yazeed Alkheriji, Andrew Salama, Xaralabos Varelas, Maria Kukuruzinska, Stefano Monti, Manish V Bais
Lysine-specific demethylase 1 (LSD1) is a nuclear histone demethylase and a member of the amine oxidase (AO) family. LSD1 is a flavin-containing AO that specifically catalyzes the demethylation of mono- and di-methylated histone H3 lysine 4 through an FAD-dependent oxidative reaction. LSD1 is inappropriately upregulated in lung, liver, brain and esophageal cancers, where it promotes cancer initiation, progression, and metastasis. However, unlike other lysine-specific demethylases, the role and specific targets of LSD1 in oral squamous cell carcinoma (OSCC) pathogenesis remain unknown...
July 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28772031/local-microrna-133a-downregulation-is-associated-with-hypertrophy-in-the-dyssynchronous-heart
#15
Lars B van Middendorp, Marion Kuiper, Chantal Munts, Philippe Wouters, Jos G Maessen, Frans A van Nieuwenhoven, Frits W Prinzen
AIMS: Left bundle branch block (LBBB) creates considerable regional differences in mechanical load within the left ventricle (LV). We investigated expression of selected microRNAs (miRs) in relation to regional hypertrophy and fibrosis in LBBB hearts and their reversibility upon cardiac resynchronization therapy (CRT). METHODS AND RESULTS: Eighteen dogs were followed for 4 months after induction of LBBB, 10 of which received CRT after 2 months. Five additional dogs served as control...
August 2017: ESC Heart Failure
https://www.readbyqxmd.com/read/28757911/baicalin-ameliorates-experimental-liver-cholestasis-in-mice-by-modulation-of-oxidative-stress-inflammation-and-nrf2-transcription-factor
#16
Kezhen Shen, Xiaowen Feng, Hao Pan, Feng Zhang, Haiyang Xie, Shusen Zheng
Experimental cholestatic liver fibrosis was performed by bile duct ligation (BDL) in mice, and significant liver injury was observed in 15 days. Administration of baicalin in mice significantly ameliorates liver fibrosis. Experimental cholestatic liver fibrosis was associated with induced gene expression of fibrotic markers such as collagen I, fibronectin, alpha smooth muscle actin (SMA), and connective tissue growth factor (CTGF); increased inflammatory cytokines (TNFα, MIP1α, IL1β, and MIP2); increased oxidative stress and reactive oxygen species- (ROS-) inducing enzymes (NOX2 and iNOS); dysfunctional mitochondrial electron chain complexes; and apoptotic/necrotic cell death markers (DNA fragmentation, caspase 3 activity, and PARP activity)...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28753062/long-noncoding-rna-h19-acts-as-a-competing-endogenous-rna-to-mediate-ctgf-expression-by-sponging-mir-455-in-cardiac-fibrosis
#17
Zhi-Wen Huang, Li-Hong Tian, Bin Yang, Run-Min Guo
Cardiac fibrosis is closely related to multiple cardiovascular system diseases, and noncoding RNAs (ncRNAs), including long noncoding RNA (lncRNA) and microRNA (miRNA), have been reported to play a vital role in fibrogenesis. The present study aims to investigate the potential regulatory mechanism of lncRNA H19 and miR-455 on fibrosis-associated protein synthesis in cardiac fibroblasts (CFs). miRNA microarray assay revealed 34 significantly dysregulated miRNAs, including 13 upregulated miRNAs and 21 downregulated miRNAs...
July 28, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28736081/frizzled-7-mediates-tgf-%C3%AE-induced-pulmonary-fibrosis-by-transmitting-non-canonical-wnt-signaling
#18
Shuhong Guan, Jun Zhou
Pulmonary fibrosis is a progressive and often fatal lung disease characterized by fibroblast proliferation and excessive deposition of extracellular matrix. Both TGF-β and Wnt signaling have been implicated in the regulation of organ fibrosis. However little is known about whether TGF-β-induced gene expression changes in Wnt signaling pathway could predict disease progression. In the study, we investigated the interaction between TGF-β and Wnt signaling in mediating pulmonary fibrosis by big data analysis, in vitro and in vivo experimental studies and clinical data analysis...
July 20, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28735624/the-effect-of-prostaglandin-e2-receptor-ptger2-activation-on-growth-factor-expression-and-cell-proliferation-in-bovine-endometrial-explants
#19
Shuangyi Zhang, Bo Liu, Wei Mao, Qianru Li, Changqi Fu, Nan Zhang, Ying Zhang, Long Gao, Yuan Shen, Jinshan Cao
The domestic animal endometrium undergoes regular periods of regeneration and degeneration during cycles of oestrus and dioestrus. If blastocyst implantation occurs in the uterus, the endometrium will prepare for pregnancy by changing its pattern of development to build a connection with the embryo to nourish it. Prostaglandin E2 (PGE2) secretion synchronized with endometrial growth in these processes and could be involved in endometrial growth. One of the PGE2 receptors (PTGER2) is present in endometrium and its increased expression accompanies with endometrial growth in above processes...
July 2017: Prostaglandins, Leukotrienes, and Essential Fatty Acids
https://www.readbyqxmd.com/read/28731126/mir%C3%A2-132-in-atrial-fibrillation-directly-targets-connective-tissue-growth-factor
#20
Gang Qiao, Dongsheng Xia, Zhaoyun Cheng, Guobao Zhang
Atrial fibrillation (AF) is the most frequently occurring, persistent cardiac arrhythmia, and the hallmark of AF‑dependent structural remodeling is atrial fibrosis. Connective tissue growth factor (CTGF) is important in the process of fibrosis. The association between miRNA and CTGF in AF‑dependent fibrosis remains to be elucidated. The present study aimed to determine if microRNA (miR)‑132 was able to regulate CTGF with an anti‑fibrotic effect in AF. A total of ten dogs or patients were assigned to control (n=4) and AF groups (n=6)...
July 21, 2017: Molecular Medicine Reports
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