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https://www.readbyqxmd.com/read/28346614/crosstalk-between-transforming-growth-factor-beta-2-and-toll-like-receptor-4-in-the-trabecular-meshwork
#1
Humberto Hernandez, Wanda E Medina-Ortiz, Tomi Luan, Abbot F Clark, Colleen M McDowell
Purpose: The trabecular meshwork (TM) is involved in the outflow of aqueous humor and intraocular pressure (IOP) regulation. Regulation of the extracellular matrix (ECM) by TGFβ2 signaling pathways in the TM has been extensively studied. Recent evidence has implicated toll-like receptor 4 (TLR4) in the regulation of ECM and fibrogenesis in liver, kidney, lung, and skin. Here, we investigated the role of TGFβ2-TLR4 signaling crosstalk in the regulation of the ECM in the TM and ocular hypertension...
March 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28342321/improvement-of-paracellular-transport-in-the-caco-2-drug-screening-model-using-protein-engineered-substrates
#2
Rebecca L DiMarco, Daniel R Hunt, Ruby E Dewi, Sarah C Heilshorn
The Caco-2 assay has achieved wide popularity among pharmaceutical companies in the past two decades as an in vitro method for estimation of in vivo oral bioavailability of pharmaceutical compounds during preclinical characterization. Despite its popularity, this assay suffers from a severe underprediction of the transport of drugs which are absorbed paracellularly, that is, which pass through the cell-cell tight junctions of the absorptive cells of the small intestine. Here, we propose that simply replacing the collagen I matrix employed in the standard Caco-2 assay with an engineered matrix, we can control cell morphology and hence regulate the cell-cell junctions that dictate paracellular transport...
March 18, 2017: Biomaterials
https://www.readbyqxmd.com/read/28341255/damage-associated-molecular-patterns-damps-released-after-burn-are-associated-with-inflammation-and-monocyte-activation
#3
Meenakshi Rani, Susannah E Nicholson, Qiong Zhang, Martin G Schwacha
Burns are associated with activation of the innate immunity that can contribute to complications. Damage-associated molecular patterns (DAMPs) released after tissue injury play a critical role in the activation of the innate immunity, which appears to be mediated via toll-like receptors (TLRs). Previous findings have shown that TLRs and TLR-mediated responses are up-regulated after burn. Nonetheless, it is unclear what impact burn has on circulating levels of DAMPs. To study this, male C57BL/6 mice were subjected to a major burn or sham procedure...
March 2017: Burns: Journal of the International Society for Burn Injuries
https://www.readbyqxmd.com/read/28341147/cadmium-stimulates-myofibroblast-differentiation-and-mouse-lung-fibrosis
#4
Xin Hu, Jolyn Fernandes, Dean P Jones, Young-Mi Go
Increasing evidence suggests that Cd at levels found in the human diet can cause oxidative stress and activate redox-sensitive transcription factors in inflammatory signaling. Following inflammation, tissue repair often involves activation of redox-sensitive transcription factors in fibroblasts. In lungs, epithelial barrier remodeling is required to restore gas exchange and barrier function, and aberrant myofibroblast differentiation leads to pulmonary fibrosis. Contributions of exogenous exposures, such as dietary Cd, to pulmonary fibrosis remain incompletely defined...
March 21, 2017: Toxicology
https://www.readbyqxmd.com/read/28340512/activation-mechanisms-of-%C3%AE-v%C3%AE-3-integrin-by-binding-to-fibronectin-a-computational-study
#5
Lingyun Wang, Di Pan, Qi Yan, Yuhua Song
Integrin αVβ3 plays an important role in regulating cellular activities and in human diseases. Although the structure of αVβ3 has been studied by crystallography and electron microscopy, the detailed activation mechanism of integrin αVβ3 induced by fibronectin (Fn) remains unclear. In this study, we investigated the conformational and dynamical motion changes of Mn(2+) -bound integrin αVβ3 by binding to Fn with molecular dynamics simulations. Results showed that Fn binding to integrin αVβ3 caused the changes of the conformational flexibility of αVβ3 domains, the essential mode of motion for the domains of αV subunit and β3 subunit and the degrees of correlated motion of residues between the domains of αV subunit and β3 subunit of integrin αVβ3...
March 24, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28339056/nobiletin-inhibits-invasion-via-inhibiting-akt-gsk3%C3%AE-%C3%AE-catenin-signaling-pathway-in-slug-expressing-glioma-cells
#6
Xiang Zhang, Kebin Zheng, Chunhui Li, Yonghui Zhao, Heyang Li, Xuguang Liu, Yinbo Long, Junchao Yao
Epithelial-mesenchymal transition (EMT) is a pivotal event in tumor progression during which cancer cells undergo dramatic changes acquiring highly invasive properties. In this study, we found that nobiletin, a polymethoxylated flavone, suppressed migration and invasion in both U87 and U251 glioma cells. Expression of epithelial markers (E-cadherin and occludin) was upregulated; mesenchymal markers (N-cadherin, fibronectin) and the transcriptional factor Slug were downregulated after nobiletin treatment. Transforming growth factor β (TGF-β) was applied to stimulate EMT and the results showed that nobiletin not only influenced basal level cell migration but also prevented TGF-β-triggered migration and EMT, with the AKT/GSK3β/β-catenin signaling pathway greatly involved...
March 23, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28339009/identification-of-egflam-spatc1l-and-rnase13-as-novel-susceptibility-loci-for-aortic-aneurysm-in-japanese-individuals-by-exome-wide-association-studies
#7
Yoshiji Yamada, Jun Sakuma, Ichiro Takeuchi, Yoshiki Yasukochi, Kimihiko Kato, Mitsutoshi Oguri, Tetsuo Fujimaki, Hideki Horibe, Masaaki Muramatsu, Motoji Sawabe, Yoshinori Fujiwara, Yu Taniguchi, Shuichi Obuchi, Hisashi Kawai, Shoji Shinkai, Seijiro Mori, Tomio Arai, Masashi Tanaka
We performed an exome-wide association study (EWAS) to identify genetic variants - in particular, low‑frequency or rare variants with a moderate to large effect size - that confer susceptibility to aortic aneurysm with 8,782 Japanese subjects (456 patients with aortic aneurysm, 8,326 control individuals) and with the use of Illumina HumanExome-12 DNA Analysis BeadChip or Infinium Exome-24 BeadChip arrays. The correlation of allele frequencies for 41,432 single nucleotide polymorphisms (SNPs) that passed quality control to aortic aneurysm was examined with Fisher's exact test...
March 21, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28337441/pentoxifylline-regulates-plasminogen-activator-inhibitor-1-expression-and-protein-kinase-a-phosphorylation-in-radiation-induced-lung-fibrosis
#8
Jong-Geol Lee, Sehwan Shim, Min-Jung Kim, Jae Kyung Myung, Won-Suk Jang, Chang-Hwan Bae, Sun-Joo Lee, Kyeong Min Kim, Young-Woo Jin, Seung-Sook Lee, Sunhoo Park
Purpose. Radiation-induced lung fibrosis (RILF) is a serious late complication of radiotherapy. In vitro studies have demonstrated that pentoxifylline (PTX) has suppressing effects in extracellular matrix production in fibroblasts, while the antifibrotic action of PTX alone using clinical dose is yet unexplored. Materials and Methods. We used micro-computed tomography (micro-CT) and histopathological analysis to evaluate the antifibrotic effects of PTX in a rat model of RILF. Results. Micro-CT findings showed that lung density, volume loss, and mediastinal shift are significantly increased at 16 weeks after irradiation...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28331417/%C3%AE-tocotrienol-inhibits-tgf-%C3%AE-1-induced-contractile-phenotype-expression-of-human-airway-smooth-muscle-cells
#9
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/28331184/the-long-non-coding-rna-linc01013-enhances-invasion-of-human-anaplastic-large-cell-lymphoma
#10
I-Hsiao Chung, Pei-Hsuan Lu, Yang-Hsiang Lin, Ming-Ming Tsai, Yun-Wen Lin, Chau-Ting Yeh, Kwang-Huei Lin
Anaplastic large-cell lymphoma (ALCL) is a rare type of highly malignant, non-Hodgkin lymphoma (NHL). Currently, only studies on the chimeric oncogene NPM-ALK have reported a link to ALCL progression. However, the specific molecular mechanisms underlying the invasion of ALCL are still unclear. Here, we sought to investigate differentially expressed, long non-coding RNAs (lncRNAs) in ALCL and their potential biological function. Our microarray analyses revealed that LINC01013, a novel non-coding RNA gene, was highly expressed in clinical specimens of ALCL and was significantly upregulated in invasive ALCL cell lines...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28331066/ketamine-induced-bladder-fibrosis-involves-epithelial-to-mesenchymal-transition-mediated-by-transforming-growth-factor-%C3%AE-1
#11
Junpeng Wang, Yang Chen, Di Gu, Guihao Zhang, Jiawei Chen, Jie Zhao, Peng Wu
Bladder wall fibrosis is a major complication of ketamine-induced cystitis (KC), but the underlying pathogenesis is poorly understood. The aim of the present study was to elucidate the mechanism of ketamine-induced fibrosis in association with epithelial-to-mesenchymal transition (EMT) mediated by transforming growth factor-β1 (TGF-β1). Sprague-Dawley rats were randomly distributed into four groups, which received saline, ketamine, ketamine combined with a TGF-β receptor (TβR) inhibitor (SB505124) for 16 weeks, or 12 weeks of ketamine and 4 weeks of abstinence...
March 22, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28327528/anti-obesity-effect-of-bombus-ignitus-queen-glycosaminoglycans-in-rats-on-a-high-fat-diet
#12
Mi Young Ahn, Ban Ji Kim, Ha Jeong Kim, Hyung Joo Yoon, Sang Duck Jee, Jae Sam Hwang, Kun-Koo Park
The mechanism of functional insect glycosaminoglycan (GAG) on obesity caused a high fat diet has not yet been elucidated. Therefore, insect glycosaminoglycans derived from Isaria sinclairii, Bombus ignitus (a type of bumblebee) queen, and Gryllus bimaculatus were purified and investigated as a potential functional food. 14-week old male Wistar rats were fed a high-fat diet (HFD) for 6 weeks. There were five groups that received daily intraperitoneal administration of phosphate buffered saline (PBS, control), GbG (GAG from Gryllus bimaculatus) 10 mg/kg, ISG (GAG from Isaria sinclairii) 10 mg/kg, IQG (GAG from Bombus ignites) 10 mg/kg, or Pravastatin (2 mg/kg)...
March 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28327179/pterostilbene-prevents-akt-erk-axis-mediated-polymerization-of-surface-fibronectin-on-suspended-lung-cancer-cells-independently-of-apoptosis-and-suppresses-metastasis
#13
Ying-Jan Wang, Jing-Fang Lin, Li-Hsin Cheng, Wen-Tsan Chang, Ying-Hsien Kao, Ming-Min Chang, Bour-Jr Wang, Hung-Chi Cheng
BACKGROUND: Polymeric fibronectin (polyFN) assembled on suspended breast cancer cells is required for metastasis. Conceivably, drugs that target such polyFN may fight against cancer metastasis. While stilbene analogs trigger pro-apoptotic effect on attached cancer cells, whether they prevent polyFN assembly and metastasis of suspended cancer cells via an apoptosis-independent manner remains unexplored. METHODS: We depleted suspended Lewis lung carcinoma (LLC) cells of polyFN by silencing the endogenous FN expression or pterostilbene (PS) to examine whether metastasis of lung cancer cells could thus be suppressed...
March 21, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28327178/glyceraldehyde-3-phosphate-dehydrogenase-acts-as-an-adhesin-in-erysipelothrix-rhusiopathiae-adhesion-to-porcine-endothelial-cells-and-as-a-receptor-in-recruitment-of-host-fibronectin-and-plasminogen
#14
Weifeng Zhu, Qiang Zhang, Jingtao Li, Yanmin Wei, Chengzhi Cai, Liang Liu, Zhongmin Xu, Meilin Jin
Erysipelothrix rhusiopathiae is the causative agent of animal erysipelas and human erysipeloid. Previous studies suggested glyceraldehyde 3-phosphate dehydrogenase (GAPDH) plays a role in the pathogenesis of E. rhusiopathiae infection. We studied E. rhusiopathiae GAPDH interactions with pig vascular endothelial cells, fibronectin, and plasminogen. Recombinant GAPDH (rGAPDH) was successfully obtained, and it was shown that it plays a role in E. rhusiopathiae adhesion to pig vascular endothelial cells. Moreover, rGAPDH could bind fibronectin and plasminogen in a dose-dependent manner...
March 21, 2017: Veterinary Research
https://www.readbyqxmd.com/read/28326171/large-scale-isolation-and-cytotoxicity-of-extracellular-vesicles-derived-from-activated-human-natural-killer-cells
#15
Ambrose Y Jong, Chun-Hua Wu, Jingbo Li, Jianping Sun, Muller Fabbri, Alan S Wayne, Robert C Seeger
Extracellular vesicles (EVs) have been the focus of great interest, as they appear to be involved in numerous important cellular processes. They deliver bioactive macromolecules such as proteins, lipids, and nucleic acids, allowing intercellular communication in multicellular organisms. EVs are secreted by all cell types, including immune cells such as natural killer cells (NK), and they may play important roles in the immune system. Currently, a large-scale procedure to obtain functional NK EVs is lacking, limiting their use clinically...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28325946/epigenetically-regulated-fibronectin-leucine-rich-transmembrane-protein-2-flrt2-shows-tumor-suppressor-activity-in-breast-cancer-cells
#16
Hansol Bae, Byungtak Kim, Hyunkyung Lee, Seungyeon Lee, Han-Sung Kang, Sun Jung Kim
To identify dysregulated genes by abnormal methylation and expression in breast cancer, we genome-wide analyzed methylation and expression microarray data from the Gene Expression Omnibus and the Cancer Genome Atlas database. One of the genes screened in silico, FLRT2, showed hypermethylation and downregulation in the cancer dataset and the association was verified both in cultured cell lines and cancer patients' tissue. To investigate the role of FLRT2 in breast cancer, its expression was knocked down and upregulated in mammary cell lines, and the effect was examined through three levels of approach: pathway analysis; cell activities such as proliferation, colony formation, migration, and adhesion; target gene expression...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28325836/fibronectins-containing-extradomain-a-or-b-enhance-osteoblast-differentiation-via-distinct-integrins
#17
Carla Sens, Katrin Huck, Stefan Pettera, Stephan Uebel, Guido Wabnitz, Markus Moser, Inaam A Nakchbandi
Fibronectin is a multidomain protein secreted by various cell types. It forms a network of fibers within the extracellular matrix, and impacts intracellular processes by binding to various molecules, primarily integrin receptors on the cells. Both the presence of several isoforms and the ability of the various domains and isoforms to bind to a variety of integrins result in a wide range of effects. In vivo findings suggest that fibronectin isoforms produced by the osteoblasts enhance their differentiation. Here we report that the isoform characterized by the presence of extra-domain A (EDA) activates α4β1 integrin and augments osteoblast differentiation...
March 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28323870/contribution-of-sortase-srta2-to-lactobacillus-casei-bl23-inhibition-of-staphylococcus-aureus-internalization-into-bovine-mammary-epithelial-cells
#18
Renata F S Souza, Julien Jardin, Chantal Cauty, Lucie Rault, Damien S Bouchard, Luis G Bermúdez-Humarán, Philippe Langella, Vicente Monedero, Núbia Seyffert, Vasco Azevedo, Yves Le Loir, Sergine Even
Probiotics have been considered as a promising strategy to prevent various diseases in both humans and animals. This approach has gained interest in recent years as a potential means to control bovine mastitis. In a previous study, we found that several L. casei strains, including BL23, were able to inhibit the internalization of S. aureus, a major etiologic agent of mastitis, into bovine mammary epithelial cells (bMEC). This antagonism required a direct contact between L. casei and bMEC or S. aureus, suggesting the inhibition relied on interactions between L...
2017: PloS One
https://www.readbyqxmd.com/read/28323212/recombinant-expression-of-epinephelus-lanceolatus-serum-amyloid-a-elsaa-and-analysis-of-its-macrophage-modulatory-activities
#19
Bor-Chyuan Su, Wen-Chun Lin, Han-Ning Huang, Jyh-Yih Chen
Serum amyloid A (SAA) is an acute-phase protein that plays a crucial role in the inflammatory response. In this study, we identified an SAA homolog from Epinephelus lanceolatus (ElSAA). Molecular characterization revealed that ElSAA contains a fibronectin-like motif that is typical of SAAs. Recombinant ElSAA protein (rElSAA) was produced in E. coli BL21 (DE3) cells and purified as a soluble protein. To analyze its biological activity, mouse Raw264.7 macrophage cells were treated with various concentrations of rElSAA...
March 18, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28322543/titratable-avidity-reduction-enhances-affinity-discrimination-in-mammalian-cellular-selections-of-yeast-displayed-ligands
#20
Lawrence A Stern, Cliff M Csizmar, Daniel R Woldring, Carston R Wagner, Benjamin J Hackel
Yeast surface display selections against mammalian cell monolayers have proven effective in isolating proteins with novel binding activity. Recent advances in this technique allow for recovery of clones with even micromolar binding affinity. However, no efficient method has been shown for affinity based selection in this context. This study demonstrates the effectiveness of titratable avidity reduction using dithiothreitol (DTT) to achieve this goal. A series of epidermal growth factor receptor binding fibronectin domains with a range of affinities are used to quantitatively identify the number of ligands per yeast cell that yield the strongest selectivity between strong, moderate, and weak affinities...
March 21, 2017: ACS Combinatorial Science
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