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Paracrine activity

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https://www.readbyqxmd.com/read/28802143/extrinsic-control-of-wnt-signaling-in-the-intestine
#1
REVIEW
Stefan Koch
The canonical Wnt/β-catenin signaling pathway is a central regulator of development and tissue homeostasis. In the intestine, Wnt signaling is primarily known as the principal organizer of epithelial stem cell identity and proliferation. Within the last decade, numerous scientific breakthroughs have shed light on epithelial self-organization in the gut, and organoids are now routinely used to study stem cell biology and intestinal pathophysiology. The contribution of non-epithelial cells to Wnt signaling in the gut has received less attention...
August 5, 2017: Differentiation; Research in Biological Diversity
https://www.readbyqxmd.com/read/28801055/therapy-with-mesenchymal-stromal-cells-or-conditioned-medium-reverse-cardiac-alterations-in-a-high-fat-diet-induced-obesity-model
#2
P S Daltro, B C Barreto, P G Silva, P Chenaud Neto, P H F Sousa Filho, D Santana Neta, G B Carvalho, D N Silva, B D Paredes, A C de Alcantara, L A R Freitas, R D Couto, R R Santos, B S F Souza, M B P Soares, S G Macambira
BACKGROUND: Obesity is associated with numerous cardiac complications, including arrhythmias, cardiac fibrosis, remodeling and heart failure. Here we evaluated the therapeutic potential of mesenchymal stromal cells (MSCs) and their conditioned medium (CM) to treat cardiac complications in a mouse model of high-fat diet (HFD)-induced obesity. METHODS: After obesity induction and HFD withdrawal, obese mice were treated with MSCs, CM or vehicle. Cardiac function was assessed using electrocardiography, echocardiography and treadmill test...
August 8, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28797930/%C3%AE-tocotrienol-induced-disruption-of-lipid-rafts-in-human-breast-cancer-cells-is-associated-with-a-reduction-in-exosome-heregulin-content
#3
Osama A Alawin, Rayan A Ahmed, Venkateshwararao Dronamraju, Karen P Briski, Paul W Sylvester
Overexpression of heregulin, a potent ligand that activates HER3 and HER4 receptors, plays a significant role in the development of chemotherapy resistance in breast cancer patients. Exosomes released from cancer cells are small vesicles originating from the outward budding of lipid rafts that carry various mitogenic proteins that then act locally in an autocrine/paracrine manner to stimulate cancer cell growth. Since the anticancer activity of γ-tocotrienol has been shown to be mediated in part through the disruption of lipid rafts, studies were conducted to determine the effect of γ-tocotrienol on exosomes mitogenic biopotency...
July 10, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28797028/characterisation-of-the-cancer-associated-glucocorticoid-system-key-role-of-11%C3%AE-hydroxysteroid-dehydrogenase-type-2
#4
Nicola Cirillo, David J Morgan, Maria Carmela Pedicillo, Antonio Celentano, Lorenzo Lo Muzio, Michael J McCullough, Stephen S Prime
BACKGROUND: Recent studies have shown that production of cortisol not only takes place in several non-adrenal peripheral tissues such as epithelial cells but, also, the local inter-conversion between cortisone and cortisol is regulated by the 11β-hydroxysteroid dehydrogenases (11β-HSDs). However, little is known about the activity of this non-adrenal glucocorticoid system in cancers. METHODS: The presence of a functioning glucocorticoid system was assessed in human skin squamous cell carcinoma (SCC) and melanoma and further, in 16 epithelial cell lines from 8 different tissue types using ELISA, western blotting and immunofluorescence...
August 10, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28794034/an-epstein-barr-virus-microrna-blocks-il-1-signaling-by-targeting-the-interleukin-1-receptor-1
#5
Camille M Skinner, Nikita S Ivanov, Sarah A Barr, Yan Chen, Rebecca L Skalsky
Epstein-Barr virus (EBV) encodes >44 viral microRNAs (miRNAs) that are differentially expressed throughout infection, can be detected in EBV-positive tumors, and manipulate several biological processes including cell proliferation, apoptosis, and immune responses. Here, we show that EBV BHRF1-2 miRNAs block NF-kB activation following treatment with pro-inflammatory cytokines, specifically interleukin-1 beta. Analysis of EBV PAR-CLIP miRNA targetome datasets combined with pathway analysis revealed multiple BHRF1-2 miRNA targets involved in interleukin signaling pathways...
August 9, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28793782/direct-activation-of-nadph-oxidase-2-by-2-deoxyribose-1-phosphate-triggers-nuclear-factor-kappa-b-dependent-angiogenesis
#6
Dina Vara, Joanna M Watt, Tiago M Fortunato, Harry Mellor, Matthew Burgess, Kate Wicks, Kimberly Mace, Shaun Reeksting, Anneke T Lubben, Caroline Pd Wheeler-Jones, Giordano Pula
AIMS: Deoxyribose-1-phosphate (dRP) is a pro-angiogenic paracrine stimulus released by cancer cells, platelets and macrophages and acting on endothelial cells. The objective of this study was to clarify how dRP stimulates angiogenic responses in human endothelial cells. RESULTS: Live cell imaging, electron paramagnetic resonance (EPR), pull-down of dRP-interacting proteins followed by immunoblotting, gene silencing of different NOXs and their regulatory co-subunits by siRNA transfection, and experiments with inhibitors of the sugar transporter GLUT1 were utilized to demonstrate that dRP acts intracellularly by directly activating the endothelial NADPH oxidase 2 (NOX2) complex, but not NOX4...
August 10, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28790030/notch-shapes-the-innate-immunophenotype-in-breast-cancer
#7
Qiang Shen, Brenda Cohen, Weiyue Zheng, Ramtin Rahbar, Bernard Martin, Kiichi Murakami, Sara Lamorte, Patrycja Thompson, Hal Berman, Juan Carlos Zúñiga-Pflücker, Pamela S Ohashi, Michael Reedijk
Notch activation, which is associated with basal-like breast cancer (BLBC), normally directs tissue patterning, suggesting that it may shape the tumor microenvironment (TME). Here we show that Notch in tumor cells regulates the expression of two powerful pro-inflammatory cytokines, IL1β and CCL2, and the recruitment of tumor-associated macrophages (TAMs). Notch also regulates TGFβ-mediated activation of tumor cells by TAMs, closing a Notch-dependent paracrine signaling loop between these two cell types. We use a novel mouse model in which Notch can be regulated in spontaneous mammary carcinoma to confirm that IL1β and CCL2 production, and macrophage recruitment are Notch-dependent...
August 8, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28779979/cancer-secretome-and-inflammation-the-bright-and-the-dark-sides-of-nf-%C3%AE%C2%BAb
#8
REVIEW
Daria Capece, Daniela Verzella, Alessandra Tessitore, Edoardo Alesse, Carlo Capalbo, Francesca Zazzeroni
Tumour promoting inflammation is widely recognized as a hallmark of cancer. The source of this chronic inflammation in cancer has been ascribed to the progressive activation over time of immune cells, mostly of the innate arm of the immune system. However, recent evidence has shown that chronic inflammation may also derive, at least in part, from senescent cells. Hence, due to the prominent role of inflammation in cancer, the cancer secretome definition includes all the secretory factors ensuing from the crosstalk between the cancer cell and the tumour microenvironment...
August 2, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28775169/loss-of-igf2-gene-imprinting-in-murine-prostate-promotes-widespread-neoplastic-growth
#9
Nathan Damaschke, Bing Yang, Sachin Bhusari, Mele Avilla, Weixiong Zhong, Michael L Blute, Wei Huang, David F Jarrard
Loss of imprinting (LOI) is an epigenetic event which relaxes an allele-specific restriction on gene expression. One gene that experiences LOI is the paracrine insulin-like growth factor IGF2, which occurs commonly in human prostate tissues during aging and tumorigenesis. However, the relationship between IGF2 LOI and prostate tumorigenesis has not been established functionally. In this study, we created a mouse model with CTCF binding site mutations at the Igf2-H19 imprint control region that abolishes CTCF insulator activity, resulting in biallelic Igf2 expression that mimics increased levels seen with aging-induced LOI...
August 3, 2017: Cancer Research
https://www.readbyqxmd.com/read/28774797/mesenchymal-stroma-role-in-osteosarcoma-progression
#10
Margherita Cortini, Sofia Avnet, Nicola Baldini
The initiation and progression of malignant tumors are supported by their microenvironment: cancer cells per se cannot explain growth and formation of the primary or metastasis, and a combination of proliferating tumor cells, cancer stem cells, immune cells mesenchymal stromal cells and/or cancer-associated fibroblasts all contribute to the tumor bulk. The interaction between these multiple players, under different microenvironmental conditions of biochemical and physical stimuli (i.e. oxygen tension, pH, matrix mechanics), regulates the production and biological activity of several soluble factors, extracellular matrix components, and extracellular vesicles that are needed for growth, maintenance, chemoresistance and metastatization of cancer...
July 31, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28774569/the-condition-medium-of-mesenchymal-stem-cells-promotes-proliferation-adhesion-and-neuronal-differentiation-of-retinal-progenitor-cells
#11
Mingqi Zhang, Fenglei Zhang, Jin Sun, Yan Sun, Ling Xu, Donglei Zhang, Zhuoshi Wang, Wei He
Retinal progenitor cell is a promising candidate in the treatment of retinal pigmentosa diseases. The limiting factors of stem cell transplantation are the proliferation and differentiation capacities of hRPCs, which may be governed by culture conditions. Previous studies have proved that the secretome of human Umbilical Cord Mesenchymal stem cells (hUCMSCs) and human Adipose derived stem cells (hADSCs), including more active cytokines and neurotrophic factors, have the paracrine potential of enhancing proliferation and differentiation in several cell types...
July 31, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28771454/%C3%AE-ketoglutarate-drives-electroneutral-nacl-reabsorption-in-intercalated-cells-by-activating-a-g-protein-coupled-receptor-oxgr1
#12
Paul R Grimm, Paul A Welling
PURPOSE OF REVIEW: This review describes the recent discoveries about a powerful electroneutral NaCl reabsorption mechanism in intercalated cells, and its regulation by an intrarenal metabolite paracrine, α-ketoglutartate, and the G-protein coupled receptor, Oxgr1. RECENT FINDINGS: The distal nephron fine-tunes sodium, chloride, potassium, hydrogen, bicarbonate and water transport to maintain electrolyte homeostasis and blood pressure. Intercalated cells have been traditionally viewed as the professional regulators of acid-base balance, but recent studies reveal that a specific population of intercalated cells, identified by the pendrin-transporter, have a surprising role in the regulation of salt balance...
September 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/28770522/hoffa-s-fat-pad-abnormality-in-the-development-of-knee-osteoarthritis
#13
Wojciech Paduszyński, Mateusz Jeśkiewicz, Paweł Uchański, Sebastian Gackowski, Marek Radkowski, Urszula Demkow
Over the past two decades, many hypotheses have been put forward to explain the cause of knee osteoarthritis. Scientific reports bring up the role of adipose tissue in the activation of the inflammatory mechanisms, which is a characteristic feature of osteoarthritis natural history. Adipose tissue produces and releases cytokines, interleukins, and growth factors by means of paracrine, endocrine, and autocrine mechanisms. Hoffa's fat pad (infrapatellar adipose tissue) plays a viable role in the initiation and progression of osteoarthritis due to its role in the activation and release of pro-inflammatory mediators...
August 3, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28768908/nonmyocyte-erk1-2-signaling-contributes-to-load-induced-cardiomyopathy-in-marfan-mice
#14
Rosanne Rouf, Elena Gallo MacFarlane, Eiki Takimoto, Rahul Chaudhary, Varun Nagpal, Peter P Rainer, Julia G Bindman, Elizabeth E Gerber, Djahida Bedja, Christopher Schiefer, Karen L Miller, Guangshuo Zhu, Loretha Myers, Nuria Amat-Alarcon, Dong I Lee, Norimichi Koitabashi, Daniel P Judge, David A Kass, Harry C Dietz
Among children with the most severe presentation of Marfan syndrome (MFS), an inherited disorder of connective tissue caused by a deficiency of extracellular fibrillin-1, heart failure is the leading cause of death. Here, we show that, while MFS mice (Fbn1C1039G/+ mice) typically have normal cardiac function, pressure overload (PO) induces an acute and severe dilated cardiomyopathy in association with fibrosis and myocyte enlargement. Failing MFS hearts show high expression of TGF-β ligands, with increased TGF-β signaling in both nonmyocytes and myocytes; pathologic ERK activation is restricted to the nonmyocyte compartment...
August 3, 2017: JCI Insight
https://www.readbyqxmd.com/read/28761088/shift-of-emt-gradient-in-3d-spheroid-mscs-for-activation-of-mesenchymal-niche-function
#15
Sohee Jeon, Ho-Sun Lee, Ga-Young Lee, Gyeongsin Park, Tae-Min Kim, Jihye Shin, Cheolju Lee, Il-Hoan Oh
Despite the wide use of mesenchymal stromal cells (MSCs) for paracrine support in clinical trials, their variable and heterogeneous supporting activity pose major challenges. While three-dimensional (3D) MSC cultures are emerging as alternative approaches, key changes in cellular characteristics during 3D-spheroid formation remain unclear. Here, we show that MSCs in 3D spheroids undergo further progression towards the epithelial-mesenchymal transition (EMT), driven by upregulation of EMT-promoting microRNAs and suppression of EMT-inhibitory miRNAs...
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28759028/innate-immune-sensing-of-cytosolic-chromatin-fragments-through-cgas-promotes-senescence
#16
Selene Glück, Baptiste Guey, Muhammet Fatih Gulen, Katharina Wolter, Tae-Won Kang, Niklas Arndt Schmacke, Anne Bridgeman, Jan Rehwinkel, Lars Zender, Andrea Ablasser
Cellular senescence is triggered by various distinct stresses and characterized by a permanent cell cycle arrest. Senescent cells secrete a variety of inflammatory factors, collectively referred to as the senescence-associated secretory phenotype (SASP). The mechanism(s) underlying the regulation of the SASP remains incompletely understood. Here we define a role for innate DNA sensing in the regulation of senescence and the SASP. We find that cyclic GMP-AMP synthase (cGAS) recognizes cytosolic chromatin fragments in senescent cells...
July 31, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28757877/trophic-activity-and-phenotype-of-adipose-tissue-derived-mesenchymal-stem-cells-as-a-background-of-their-regenerative-potential
#17
REVIEW
Beata Kocan, Aleksandra Maziarz, Jacek Tabarkiewicz, Takahiro Ochiya, Agnieszka Banaś-Ząbczyk
There has been an increased interest in mesenchymal stem cells from adipose tissue, due to their abundance and accessibility with no ethical concerns. Their multipotent properties make them appropriate for regenerative clinical applications. It has been shown that adipose-derived stem cells (ASCs) may differ between the origin sites. Moreover, a variety of internal and external factors may affect their biological characteristics, as what we aimed to highlight in this review. It has been demonstrated that ASCs secrete multiple trophic factors that are capable of stimulating cell proliferation and differentiation and migration of various cell types...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28757246/evaluation-of-mesenchymal-stem-cell-modulation-of-trigeminal-neuronal-responses-to-cold
#18
Michael A Eskander, Koyo Takimoto, Anibal Diogenes
Tissue engineering protocols, such as regenerative endodontic procedures (REPs), comprise biologically based procedures designed to restore normal physiologic function. For REPs, the goal is reconstitution of the pulp-dentin complex by delivering mesenchymal stem cells (MSCs), including the stem cells of the apical papilla (SCAP) into a root canal system. Many patients regain cold sensitivity after REPs, but the mechanism is not understood. We hypothesized that SCAP modulate nociceptive function through a paracrine mechanism that activates cold-sensitive ion channels in neurons...
July 27, 2017: Neuroscience
https://www.readbyqxmd.com/read/28757170/the-deleterious-interplay-between-tumor-epithelia-and-stroma-in-cholangiocarcinoma
#19
REVIEW
Massimiliano Cadamuro, Tommaso Stecca, Simone Brivio, Valeria Mariotti, Romina Fiorotto, Carlo Spirli, Mario Strazzabosco, Luca Fabris
Prognosis of cholangiocarcinoma, a devastating liver epithelial malignancy characterized by early invasiveness, remains very dismal, though its incidence has been steadily increasing. Evidence is mounting that in cholangiocarcinoma, tumor epithelial cells establish an intricate web of mutual interactions with multiple stromal components, largely determining the pervasive behavior of the tumor. The main cellular components of the tumor microenvironment (i.e. myofibroblasts, macrophages, lymphatic endothelial cells), which has been recently termed as 'tumor reactive stroma', are recruited and activated by neoplastic cells, and in turn, deleteriously mold tumor behavior by releasing a huge variety of paracrine signals, including cyto/chemokines, growth factors, morphogens and proteinases...
July 27, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28755912/examination-of-pathways-involved-in-leukemia-inhibitory-factor-lif-induced-cell-growth-arrest-using-label-free-proteomics-approach
#20
Syed Azmal Ali, Gurjeet Kaur, Ashok Kumar Mohanty, Sudarshan Kumar
Leukemia inhibitory factor (LIF) is a multifunctional highly glycosylated protein, synthesized and secreted in various body tissues. Besides the abundance in multiple organs, the molecular mechanism underlying the LIF interactions for cell survival and polarity is poorly understood. In the present study, high-resolution LC-MS/MS based LFQ approach identified 2083 proteins with the overall PSM as 16,032. This proteomics data reviles that LIF promotes the AKT-mTOR signaling pathway. It induces cell growth arrest by an intracellular pathways loop to increase the half-life of the cell...
July 26, 2017: Journal of Proteomics
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