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Paracrine activity

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https://www.readbyqxmd.com/read/28642329/experimental-and-computational-insight-into-human-mesenchymal-stem-cell-paracrine-signaling-and-heterocellular-coupling-effects-on-cardiac-contractility-and-arrhythmogenicity
#1
Joshua Mayourian, Timothy J Cashman, Delaine K Ceholski, Bryce V Johnson, David Sachs, Deepak A Kaji, Susmita Sahoo, Joshua M Hare, Roger J Hajjar, Eric A Sobie, Kevin D Costa
Rationale: Myocardial delivery of human mesenchymal stem cells (hMSCs) is an emerging therapy for treating the failing heart. However, the relative effects of hMSC-mediated heterocellular coupling (HC) and paracrine signaling (PS) on human cardiac contractility and arrhythmogenicity remain unresolved. Objective: To better understand hMSC PS and HC effects on human cardiac contractility and arrhythmogenicity by integrating experimental and computational approaches. Methods and Results: : Extending our previous hMSC-cardiomyocyte HC computational model, we incorporated experimentally calibrated hMSC PS effects on cardiomyocyte L-type calcium channel/SERCA activity and cardiac tissue fibrosis...
June 22, 2017: Circulation Research
https://www.readbyqxmd.com/read/28637870/cardiac-myocyte-p38%C3%AE-kinase-regulates-angiogenesis-via-myocyte-endothelial-cell-cross-talk-during-stress-induced-remodeling-in-heart
#2
Beth A Rose, Tomohiro Yokota, Vishnu Chintalgattu, Shuxun Ren, Luisa Iruela-Arispe, Aarif Y Khakoo, Susumu Minamisawa, Yibin Wang
Stress-induced p38 mitogen-activated protein kinase (MAPK) activity is implicated in pathological remodeling in the heart. For example, constitutive p38 MAPK activation in cardiomyocytes induces pathological features, including myocyte hypertrophy, apoptosis, contractile dysfunction, and fetal gene expression. However, the physiological function of cardiomyocyte p38 MAPK activity in beneficial compensatory vascular remodeling is unclear. This report investigated the functional role and the underlying mechanisms of cardiomyocyte p38 MAPK activity in cardiac remodeling induced by chronic stress...
June 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28635301/stem-cell-mediated-paracrine-signaling-alters-fibroplasia-in-human-vocal-fold-fibroblasts-in-vitro
#3
Nao Hiwatashi, Renjie Bing, Iv Kraja, Ryan C Branski
OBJECTIVES: Interactions between mesenchymal stem cells (MSCs) and native vocal fold fibroblasts (VFFs) have not been described in spite of promising preliminary data regarding the effects of MSCs on vocal fold repair in vivo. The current study employed a conditioned media (CM) model to investigate the paracrine effects of bone marrow-derived mesenchymal stem cells (BMSCs) on VFFs. METHODS: Human VFFs were treated with transforming growth factor-β1 (TGF-β1; 10 ng/mL), CM from human BMSCs following 48 hours of TGF-β1 stimulation, or CM+TGF-β1...
June 1, 2017: Annals of Otology, Rhinology, and Laryngology
https://www.readbyqxmd.com/read/28634726/connexin-channels-at-the-glio-vascular-interface-gatekeepers-of-the-brain
#4
Marijke De Bock, Luc Leybaert, Christian Giaume
Neuronal survival, electrical signaling and synaptic activity require a well-balanced micro-environment in the central nervous system. This is achieved by the blood-brain barrier (BBB), an endothelial barrier situated in the brain capillaries, that controls near-to-all passage in and out of the brain. The endothelial barrier function is highly dependent on signaling interactions with surrounding glial, neuronal and vascular cells, together forming the neuro-glio-vascular unit. Within this functional unit, connexin (Cx) channels are of utmost importance for intercellular communication between the different cellular compartments...
June 20, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28631889/microrna-containing-extracellular-vesicles-released-from-endothelial-colony-forming-cells-modulate-angiogenesis-during-ischaemic-retinopathy
#5
Margaret Dellett, Eoin D Brown, Jasenka Guduric-Fuchs, Anna O'Connor, Alan W Stitt, Reinhold J Medina, David A Simpson
Endothelial colony-forming cells (ECFCs) are a defined subtype of endothelial progenitors that modulate vascular repair and promote perfusion in ischaemic tissues. Their paracrine activity on resident vasculature is ill-defined, but mediated, at least in part, by the transfer of extracellular vesicles (EVs). To evaluate the potential of isolated EVs to provide an alternative to cell-based therapies, we first performed a physical and molecular characterization of those released by ECFCs. Their effects upon endothelial cells in vitro and angiogenesis in vivo in a model of proliferative retinopathy were assessed...
June 20, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28629363/fibroblast-paracrine-tnf-%C3%AE-signaling-elevates-integrin-a5-expression-in-idiopathic-pulmonary-fibrosis-ipf
#6
Gali Epstein Shochet, Elizabetha Brook, Lilach Israeli-Shani, Evgeny Edelstein, David Shitrit
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with a poor prognosis. Inflammatory cytokines play a significant role in IPF pathology. However, the fibroblast itself is also believed to be the primary effector in IPF. We hypothesized that the fibroblasts themselves secrete pro-inflammatory cytokines that could propagate IPF by affecting normal neighboring cells. Thus, we explored the effects of IPF fibroblast derived media on normal fibroblast characteristics...
June 19, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28626027/selective-activation-of-epidermal-growth-factor-receptor-in-renal-proximal-tubule-induces-tubulointerstitial-fibrosis
#7
Jessica M Overstreet, Yinqiu Wang, Xin Wang, Aolei Niu, Leslie S Gewin, Bing Yao, Raymond C Harris, Ming-Zhi Zhang
Epidermal growth factor receptor (EGFR) has been implicated in the pathogenesis of diabetic nephropathy and renal fibrosis; however, the causative role of sustained EGFR activation is unclear. Here, we generated a novel kidney fibrotic mouse model of persistent EGFR activation by selectively expressing the EGFR ligand, human heparin-binding EGF-like growth factor (HB-EGF), in renal proximal tubule epithelium. Human HB-EGF expression increased tyrosine kinase phosphorylation of EGFR and the subsequent activation of downstream signaling pathways, including ERK and AKT, as well as the profibrotic TGF-β1/SMAD pathway...
June 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28622965/tumour-derived-human-growth-hormone-as-a-therapeutic-target-in-oncology
#8
REVIEW
Jo K Perry, Zheng-Sheng Wu, Hichem C Mertani, Tao Zhu, Peter E Lobie
The growth hormone (GH) and insulin-like growth factor-1 (IGF1) axis is the key regulator of longitudinal growth, promoting postnatal bone and muscle growth. The available data suggest that GH expression by tumour cells is associated with the aetiology and progression of various cancers such as endometrial, breast, liver, prostate, and colon cancer. Accordingly there has been increased interest in targeting GH-mediated signal transduction in a therapeutic setting. Because GH has endocrine, autocrine, and paracrine actions, therapeutic strategies will need to take into account systemic and local functions...
June 13, 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/28622174/insufficient-astrocyte-derived-brain-derived-neurotrophic-factor-contributes-to-propofol-induced-neuron-death-through-akt-glycogen-synthase-kinase-3%C3%AE-mitochondrial-fission-pathway
#9
Yanan Liu, Yasheng Yan, Yasuyoshi Inagaki, Sarah Logan, Zeljko J Bosnjak, Xiaowen Bai
BACKGROUND: Growing animal evidence demonstrates that prolonged exposure to propofol during brain development induces widespread neuronal cell death, but there is little information on the role of astrocytes. Astrocytes can release neurotrophic growth factors such as brain-derived neurotrophic factor (BDNF), which can exert the protective effect on neurons in paracrine fashion. We hypothesize that during propofol anesthesia, BDNF released from developing astrocytes may not be sufficient to prevent propofol-induced neurotoxicity...
July 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28621496/adrenomedullin-regulates-the-speed-of-oviductal-fluid-flow-in-cattle
#10
Yuka Yoshimoto, Takumi Nishie, Sayaka Ito, Yoshihiko Kobayashi, Yuki Yamamoto, Kiyoshi Okuda, Koji Kimura
Unidirectional flow of oviductal fluid from the ovarian to uterine side of the ampulla plays a significant role in successful pregnancy, and is produced by ciliary beating. Various systems regulate ciliary beating, such as paracrine, autocrine, and endocrine. We hypothesized that Adrenomedullin (ADM) - a peptide hormone that acts via its receptors, which are complexes of Calcitonin receptor-like receptor (CRLR) and Receptor activity-modifying protein (RAMP) 2 or 3-promotes oviductal fluid flow in the ampulla of bovine oviducts...
June 16, 2017: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/28618839/sphingosine-kinase-and-sphingosine-1-phosphate-in-liver-pathobiology
#11
Timothy Rohrbach, Michael Maceyka, Sarah Spiegel
Over 20 years ago, sphingosine-1-phosphate (S1P) was discovered to be a bioactive signaling molecule. Subsequent studies later identified two related kinases, sphingosine kinase 1 and 2, which are responsible for the phosphorylation of sphingosine to S1P. Many stimuli increase sphingosine kinase activity and S1P production and secretion. Outside the cell, S1P can bind to and activate five S1P-specific G protein-coupled receptors (S1PR1-5) to regulate many important cellular and physiological processes in an autocrine or paracrine manner...
June 15, 2017: Critical Reviews in Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28612556/-effects-of-msp-on-the-proliferation-migration-and-invasion-of-human-non-small-cell-lung-cancer-cells
#12
Xia Liu, Shi-Hang Wei, Xue-Ni Shi, Yi-Nan Zuo, Xue-Ling He, Hai-Lin Yin
OBJECTIVES: To determine the effects of macrophage stimulating protein (Msp) on the proliferation, migration and invasion of human non-small cell lung cancer cells PC14. METHODS: The eukaryotic expression vector for st1was constructed and transfected into Msp(-)and RON(-)human non-small cell lung cancer cells PC14. The expression of st1mRNA in PC14 cells was observed by RT-PCR. The expression levels of Msp protein in PC14, PC14-st1-pEGFP-N1 and PC14-pEGFP-N1 groups as well as the expression of RON in PC14 and SKBR-3 cells were detected by Western blot...
January 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28612045/lack-of-trpm5-expressing-microvillous-cells-in-mouse-main-olfactory-epithelium-leads-to-impaired-odor-evoked-responses-and-olfactory-guided-behavior-in-a-challenging-chemical-environment
#13
Kayla Lemons, Ziying Fu, Imad Aoudé, Tatsuya Ogura, Julianna Sun, Justin Chang, Kenechukwu Mbonu, Ichiro Matsumoto, Hiroyuki Arakawa, Weihong Lin
The mammalian main olfactory epithelium (MOE) modifies its activities in response to changes in the chemical environment. This process is essential for maintaining the functions of the olfactory system and the upper airway. However, mechanisms involved in this functional maintenance, especially those occurring via paracrine regulatory pathways within the multicellular MOE, are poorly understood. Previously, a population of non-neuronal, transient receptor potential M5-expressing microvillous cells (TRPM5-MCs) was identified in the MOE, and the initial characterization of these cells showed that they are cholinergic and responsive to various xenobiotics including odorants at high concentrations...
May 2017: ENeuro
https://www.readbyqxmd.com/read/28608561/angiogenic-and-restorative-ability-of-human-mesenchymal-stem-cells-were-reduced-following-treatment-with-serum-from-diabetes-mellitus-type-2-patients
#14
Jafar Rezaie, Malek Soleimani Mehranjani, Reza Rahbarghazi, Mohammad Ali Shariatzadeh
This experiment investigated the impact of serum from patients with type 2 diabetes mellitus on the angiogenic behavior of human mesenchymal stem cells in vitro. Changes in the level of Ang-1, Ang-2, cell migration and trans-differentiation into pericytes and endothelial lineage were monitored after 7 days. The interaction of mesenchymal stem cells with endothelial cells were evaluated using surface plasmon resonance technique. Paracrine restorative effect of diabetic stem cells was tested on pancreatic β cells...
June 13, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28607130/s1pr1-sphingosine-1-phosphate-receptor-1-signaling-regulates-blood-flow-and-pressure
#15
Anna Cantalupo, Antonella Gargiulo, Elona Dautaj, Catherine Liu, Yi Zhang, Timothy Hla, Annarita Di Lorenzo
Nitric oxide is one of the major endothelial-derived vasoactive factors that regulate blood pressure (BP), and the bioactive lipid mediator S1P (sphingosine-1-phosphate) is a potent activator of endothelial nitric oxide synthase through G protein-coupled receptors. Endothelial-derived S1P and the autocrine/paracrine activation of S1PR (S1P receptors) play an important role in preserving vascular functions and BP homeostasis. Furthermore, FTY720 (fingolimod), binding to 4 out of 5 S1PRs recently approved by the Food and Drug Administration to treat autoimmune conditions, induces a modest and transient decrease in heart rate in both animals and humans, suggesting that drugs targeting sphingolipid signaling affect cardiovascular functions in vivo...
June 12, 2017: Hypertension
https://www.readbyqxmd.com/read/28607112/cutting-edge-active-tgf-%C3%AE-1-released-from-garp-tgf-%C3%AE-1-complexes-on-the-surface-of-stimulated-human-b-lymphocytes-increases-class-switch-recombination-and-production-of-iga
#16
Olivier Dedobbeleer, Julie Stockis, Bas van der Woning, Pierre G Coulie, Sophie Lucas
Production of active TGF-β is regulated at a posttranslational level and implies release of the mature cytokine dimer from the inactive, latent TGF-β precursor. There are several cell-type specific mechanisms of TGF-β activation. We identified a new mechanism operating on the surface of human regulatory T cells and involving membrane protein GARP, which binds latent TGF-β1. The paracrine activity of regulatory T cell-derived TGF-β1 contributes to immunosuppression and can be inhibited with anti-GARP Abs...
June 12, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28606996/targeting-endothelin-receptor-signalling-overcomes-heterogeneity-driven-therapy-failure
#17
Michael P Smith, Emily J Rowling, Zsofia Miskolczi, Jennifer Ferguson, Loredana Spoerri, Nikolas K Haass, Olivia Sloss, Sophie McEntegart, Imanol Arozarena, Alex von Kriegsheim, Javier Rodriguez, Holly Brunton, Jivko Kmarashev, Mitchell P Levesque, Reinhard Dummer, Dennie T Frederick, Miles C Andrews, Zachary A Cooper, Keith T Flaherty, Jennifer A Wargo, Claudia Wellbrock
Approaches to prolong responses to BRAF targeting drugs in melanoma patients are challenged by phenotype heterogeneity. Melanomas of a "MITF-high" phenotype usually respond well to BRAF inhibitor therapy, but these melanomas also contain subpopulations of the de novo resistance "AXL-high" phenotype. > 50% of melanomas progress with enriched "AXL-high" populations, and because AXL is linked to de-differentiation and invasiveness avoiding an "AXL-high relapse" is desirable. We discovered that phenotype heterogeneity is supported during the response phase of BRAF inhibitor therapy due to MITF-induced expression of endothelin 1 (EDN1)...
June 12, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28605657/muscle-as-a-paracrine-and-endocrine-organ
#18
REVIEW
Jimena Giudice, Joan M Taylor
Skeletal muscle cells are highly abundant and metabolically active and are known to 'communicate' their energy demands to other organs through active secretion. Muscle-derived secretory proteins include a variety of cytokines and peptides collectively referred to as 'myokines' that exert autocrine, paracrine or endocrine effects. Analyses of the skeletal muscle secretome revealed that numerous myokines are secreted in response to contraction or strength training, and that these factors not only regulate energy demand but also contribute to the broad beneficial effects of exercise on cardiovascular, metabolic, and mental health...
June 9, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28604807/brain-derived-neurotrophic-factor-bdnf-trkb-signaling-modulates-cancer-endothelial-cells-interaction-and-affects-the-outcomes-of-triple-negative-breast-cancer
#19
Yi-Fang Tsai, Ling-Ming Tseng, Chih-Yi Hsu, Muh-Hwa Yang, Jen-Hwey Chiu, Yi-Ming Shyr
AIMS: There is good evidence that the tumor microenvironment plays an important role in cancer metastasis and progression. Our previous studies have shown that brain-derived neurotrophic factor (BDNF) participates in the process of metastasis and in the migration of cancer cells. The aim of this study was to investigate the role of BDNF on the tumor cell microenvironment, namely, the cancer cell-endothelial cell interaction of TNBC cells. METHODS: We conducted oligoneucleotide microarray analysis of potential biomarkers that are able to differentiate recurrent TNBC from non-recurrent TNBC...
2017: PloS One
https://www.readbyqxmd.com/read/28604738/emt-cells-increase-breast-cancer-metastasis-via-paracrine-gli-activation-in-neighbouring-tumour-cells
#20
Deepika Neelakantan, Hengbo Zhou, Michael U J Oliphant, Xiaomei Zhang, Lukas M Simon, David M Henke, Chad A Shaw, Meng-Fen Wu, Susan G Hilsenbeck, Lisa D White, Michael T Lewis, Heide L Ford
Recent fate-mapping studies concluded that EMT is not required for metastasis of carcinomas. Here we challenge this conclusion by showing that these studies failed to account for possible crosstalk between EMT and non-EMT cells that promotes dissemination of non-EMT cells. In breast cancer models, EMT cells induce increased metastasis of weakly metastatic, non-EMT tumour cells in a paracrine manner, in part by non-cell autonomous activation of the GLI transcription factor. Treatment with GANT61, a GLI1/2 inhibitor, but not with IPI 926, a Smoothened inhibitor, blocks this effect and inhibits growth in PDX models...
June 12, 2017: Nature Communications
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