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https://www.readbyqxmd.com/read/28694438/stress-induces-more-serious-barrier-dysfunction-in-follicle-associated-epithelium-than-villus-epithelium-involving-mast-cells-and-protease-activated-receptor-2
#1
Lei Zhang, Jun Song, Tao Bai, Wei Qian, Xiao-Hua Hou
Psychological stress has been associated with intestinal epithelial hyperpermeability, the basic process in various functional and organic bowel diseases. In the present study, we aimed to clarify the differences and underlining mechanisms in stress-induced barrier disruption in functionally and structurally distinct epitheliums, including the villus epithelium (VE) and follicle-associated epithelium (FAE), a specialized epithelium overlaid the domes of Peyer's lymphoid follicles. Employing an Ussing Chamber system, the epithelial permeability was assessed in rats following water avoidance stress (WAS) in vivo and in mucosa tissues exposed to corticotropin-releasing factor (CRF) ex vivo...
July 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28694352/protease-activated-receptor-2-promotes-kidney-tubular-epithelial-inflammation-by-inhibiting-autophagy-via-the-pi3k-akt-mtor-signalling-pathway
#2
Chunyang Du, Tao Zhang, Xia Xiao, Yonghong Shi, Huijun Duan, Yunzhuo Ren
Protease activated receptors 2 (PAR2), which belongs to a specific class of the G-protein-coupled receptors, are central to several inflammation processes. However, the precise molecular mechanism involved remains undefined. Autophagy has been previously shown to affect inflammation. In this study, we examine the effect of PAR2 on kidney tubular epithelial autophagy and on autophagy-related inflammation and reveal the underlying mechanism involved. Autophagic activity and levels of autophagic marker LC3 were examined in human kidney tubular epithelial cells with PAR2 knockdown or overexpression...
July 10, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28643288/inhibitory-effect-of-fsllry-nh2-on-inflammatory-responses-induced-by-hydrogen-peroxide-in-hepg2-cells
#3
Yeon Joo Lee, Su Jin Kim, Kyoung Wan Kwon, Won Mo Lee, Wi Joon Im, Uy Dong Sohn
Proteinase activated receptor 2 (PAR2), which is localized in the GI tract, the respiratory system, and the kidney tubules is a G protein-coupled receptor associated with inflammation, metabolism, and disease. The aim of this study was to explore the role of PAR2 in hydrogen peroxide (H2O2)-induced HepG2 cells by using FSLLRY-NH2 a PAR2 antagonist. H2O2 treatment resulted in induction of PAR2 in esophageal, gastric, and liver cells, with the most robust response being in HepG2 cells. Furthermore, this effect was dose-dependent in HepG2 cells...
June 22, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28614190/non-histaminergic-and-mechanical-itch-sensitization-in-atopic-dermatitis
#4
H H Andersen, J Elberling, H Sølvsten, G Yosipovitch, L Arendt-Nielsen
Chronic or episodic severe itch is recurrent in atopic dermatitis (AD). Non-histaminergic neuronal itch pathways are suggested to dominate in AD itch, contributing to an "itch-scratch-itch cycle" that prolongs and worsens itch, pain, and skin lesions. We hypothesized that non-histaminergic neuronal sensitization contributes to itch in AD. Hence, we compared sensitivity to thermal, mechanical, and chemical pruritic stimuli in AD patients and controls. The study comprised 25 AD patients with chronic itch and 25 healthy controls...
June 9, 2017: Pain
https://www.readbyqxmd.com/read/28613153/precision-in-the-design-of-an-experimental-study-deflects-the-significance-of-proteinase-activated-receptor-2-expression-in-scrapie-inoculated-mice
#5
Zdenka Hanusova, Tibor Mosko, Radoslav Matej, Karel Holada
Proteinase-activated receptor 2 (PAR2) is suspected to modulate the pathogenesis of various neurodegenerative conditions. We previously described delayed onset of clinical symptoms and prolonged survival of PAR2-deficient mice after intracerebral inoculation with prions. Here we report the results from a refined blinded study that aimed to investigate the effects of PAR2 deletion on scrapie pathogenesis after peripheral infection. This study failed to confirm that PAR2 deficiency impacts on the length of the incubation period, with PAR2-/- and PAR2+/+ littermates developing scrapie at the same time...
June 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28522609/coagulation-factor-viia-mediated-protease-activated-receptor-2-activation-leads-to-%C3%AE-catenin-accumulation-via-the-akt-gsk3%C3%AE-pathway-and-contributes-to-breast-cancer-progression
#6
Abhishek Roy, Shabbir A Ansari, Kaushik Das, Ramesh Prasad, Anindita Bhattacharya, Suman Mallik, Asis Mukherjee, Prosenjit Sen
Cell migration and invasion are very characteristic features of cancer cells that promote metastasis, which is one of the most vulnerable causes of mortality among cancer patients. Emerging evidence has shown that coagulation factors can directly mediate cancer associated complications either by enhancing thrombus formation or by initiating various signaling events leading to metastatic cancer progression. It is well-established that apart from its distinct role in blood coagulation, coagulation factor FVIIa enhances aggressive behaviors of breast cancer cells, but the underlying signaling mechanisms still remain elusive...
May 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28503577/the-role-of-proteinase-activated-receptors-1-and-2-in-the-regulation-of-periodontal-tissue-metabolism-and-disease
#7
REVIEW
E S Rovai, M Holzhausen
Proteinase-activated receptors 1 (PAR1) and 2 (PAR2) are the most highly expressed members of the PAR family in the periodontium. These receptors regulate periodontal inflammatory and repair processes through their activation by endogenous and bacterial enzymes. PAR1 is expressed by the periodontal cells such as human gingival fibroblasts, gingival epithelial cells, periodontal ligament cells, osteoblasts, and monocytic cells and can be activated by thrombin, matrix metalloproteinase 1 (MMP-1), MMP-13, fibrin, and gingipains from Porphyromonas gingivalis...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28485540/proteinase-activated-receptor-2-modulates-ve-cadherin-expression-to-affect-human-vascular-endothelial-barrier-function
#8
Rui Zhang, Jianjun Ge
Published data indicate that the protease-activated receptor (PAR) 2 is involved in the pathogenesis of some cardiovascular diseases; the underlying mechanism is to be further investigated. Ve-cadherin is a critical molecule in maintaining the endothelial barrier integrity. This study aims to investigate the role of PAR2 activation in compromising the cardiac endothelial barrier function. In this study, human umbilical vein endothelial cells (Huvec cells) were cultured into monolayers using as an in vitro model of barrier function...
May 9, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28483635/crystal-structure-of-tissue-factor-in-complex-with-antibody-10h10-reveals-the-signaling-epitope
#9
Alexey Teplyakov, Galina Obmolova, Thomas J Malia, Bingyuan Wu, Yonghong Zhao, Susann Taudte, G Mark Anderson, Gary L Gilliland
Tissue factor (TF) initiates the extrinsic pathway of blood coagulation through sequential binding and activation of coagulation factors VII (FVII) and X (FX). In addition, through activation of G-protein-coupled protease activated receptors (PARs) TF induces cell signaling that is related to cancer, angiogenesis and inflammation. Monoclonal antibodies (mAbs) proved to be a useful tool for studying the interplay between TF signaling and coagulation. MAb 10H10 is unique in that it blocks the signaling pathway and thus inhibits angiogenesis and tumor growth without interfering with coagulation...
May 5, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28445455/structural-insight-into-allosteric-modulation-of-protease-activated-receptor-2
#10
Robert K Y Cheng, Cédric Fiez-Vandal, Oliver Schlenker, Karl Edman, Birte Aggeler, Dean G Brown, Giles A Brown, Robert M Cooke, Christoph E Dumelin, Andrew S Doré, Stefan Geschwindner, Christoph Grebner, Nils-Olov Hermansson, Ali Jazayeri, Patrik Johansson, Louis Leong, Rudi Prihandoko, Mathieu Rappas, Holly Soutter, Arjan Snijder, Linda Sundström, Benjamin Tehan, Peter Thornton, Dawn Troast, Giselle Wiggin, Andrei Zhukov, Fiona H Marshall, Niek Dekker
Protease-activated receptors (PARs) are a family of G-protein-coupled receptors (GPCRs) that are irreversibly activated by proteolytic cleavage of the N terminus, which unmasks a tethered peptide ligand that binds and activates the transmembrane receptor domain, eliciting a cellular cascade in response to inflammatory signals and other stimuli. PARs are implicated in a wide range of diseases, such as cancer and inflammation. PARs have been the subject of major pharmaceutical research efforts but the discovery of small-molecule antagonists that effectively bind them has proved challenging...
May 4, 2017: Nature
https://www.readbyqxmd.com/read/28441717/dexmedetomidine-relieves-formaldehyde-induced-pain-in-rats-through-both-%C3%AE-2-adrenoceptor-and-imidazoline-receptor
#11
Hong Zhang, Xiang Yan, De-Gui Wang, Yu-Fang Leng, Zhan-Hai Wan, Yong-Qiang Liu, Yan Zhang
Dexmedetomidine (DEX) is a highly selective α2 adrenergic receptor agonist. In this study, we investigated the analgesic effect and the underlying mechanisms of DEX on inflammatory visceral pain in rats. Twenty-five male Sprague Dawley (SD) rats were randomly divided into 5 groups, including control, sham, low dose DEX, medium dose DEX and high dose DEX group. Pain was induced with 10% formalin and scored every 15min till 2 h-post the induction. Hematoxylin-eosin (HE) staining was used to evaluate the toxicity of DEX on spinal cord neurons...
June 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28426164/protease-activated-receptor-2-suppresses-interleukin-il-10-expression-in-b-cells-via-upregulating-bcl2l12-in-patients-with-allergic-rhinitis
#12
J-M Xue, L-T Yang, G Yang, X-R Geng, Z-Q Liu, S Wang, H-L Zhao, Z-G Liu, C-Q Zhao, P-C Yang
BACKGROUND AND AIMS: The function of interleukin (IL)-10-producing B cells (B10 cell) is compromised in patients with allergic diseases. Protease-activated receptor (PAR)-2 has immunoregulatory functions. This study aimed to elucidate the role of PAR2 in the suppression of IL-10 expression in peripheral B cells. METHODS: Peripheral blood B cells were collected from patients with allergic rhinitis (AR). A correlation between the expression of Bcl2-like protein 12 (Bcl2L12) and IL-10 in the B cells was analyzed...
April 20, 2017: Allergy
https://www.readbyqxmd.com/read/28418856/low-density-lipoprotein-receptor-related-protein-6-is-a-novel-coreceptor-of-protease-activated-receptor-2-in-the-dynamics-of-cancer-associated-%C3%AE-catenin-stabilization
#13
Jeetendra Kumar Nag, Arun Kancharla, Myriam Maoz, Hagit Turm, Daniel Agranovich, Chhedi Lal Gupta, Beatrice Uziely, Rachel Bar-Shavit
Protease-activated receptor-2 (PAR2) plays a central role in cancer; however, the molecular machinery of PAR2-instigated tumors remains to be elucidated. We show that PAR2 is a potent inducer of β-catenin stabilization, a core process in cancer biology, leading to its transcriptional activity. Novel association of low-density lipoprotein-related protein 6 (LRP6), a known coreceptor of Frizzleds (Fz), with PAR2 takes place following PAR2 activation. The association between PAR2 and LRP6 was demonstrated employing co-immunoprecipitation, bioluminescence resonance energy transfer (BRET), and confocal microscopy analysis...
June 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28389775/erratum-to-sensitisation-of-trpv4-by-par2-is-independent-of-intracellular-calcium-signalling-and-can-be-mediated-by-the-biased-agonist-neutrophil-elastase
#14
Silvia Sostegni, Alexei Diakov, Peter McIntyre, Nigel Bunnett, Christoph Korbmacher, Silke Haerteis
No abstract text is available yet for this article.
April 7, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28381109/-express-prostanoid-dependent-spontaneous-pain-and-par2-dependent-mechanical-allodynia-following-oral-mucosal-trauma-involvement-of-trpv1-trpa1-and-trpv4
#15
Misa Ito, Kentaro Ono, Suzuro Hitomi, Tomotaka Nodai, Teppei Sago, Kiichiro Yamaguchi, Nozomu Harano, Kaori Gunnjigake, Ryuji Hosokawa, Tatsuo Kawamoto, Kiyotoshi Inenaga
No abstract text is available yet for this article.
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28374503/tryptase-potentiates-enteric-nerve-activation-by-histamine-and-serotonin-relevance-for-the-effects-of-mucosal-biopsy-supernatants-from-irritable-bowel-syndrome-patients
#16
D Ostertag, A Annahazi, D Krueger, K Michel, I E Demir, G O Ceyhan, F Zeller, M Schemann
BACKGROUND: We previously showed that mucosal biopsy supernatants from irritable bowel syndrome patients activated neurons despite low concentrations of tryptase, histamine, and serotonin which individually would not cause spike discharge. We studied the potentiating responses between these mediators on excitability of enteric neurons. METHODS: Calcium-imaging was performed using the calcium-sensitive dye Fluo-4 AM in human submucous plexus preparations from 45 individuals...
April 4, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/28349651/dermasence-refining-gel-modulates-pathogenetic-factors-of-rosacea-in-vitro
#17
C Borelli, B Becker, S Thude, B Fehrenbacher, D Isermann
BACKGROUND: Over the counter cosmetics sold for local treatment of slight to moderate rosacea often state the claim of actively modulating rosacea pathogenesis. Factors involved in the pathogenesis of this common yet complex skin disorder include kallikrein-related peptidase 5 (KLK5), LL-37, as well as protease-activated receptor 2 (PAR2) and vascular endothelial growth factor (VEGF). OBJECTIVE: The objective was to prove the modulating effect of the cosmetic skin care agent Dermasence Refining Gel (DRG) on factors involved in rosacea pathogenesis...
March 27, 2017: Journal of Cosmetic Dermatology
https://www.readbyqxmd.com/read/28323866/elevated-fecal-peptidase-d-at-onset-of-colitis-in-galphai2-mice-a-mouse-model-of-ibd
#18
Daniel Bergemalm, Robert Kruse, Maria Sapnara, Jonas Halfvarson, Elisabeth Hultgren Hörnquist
BACKGROUND: The identification of novel fecal biomarkers in inflammatory bowel disease (IBD) is hampered by the complexity of the human fecal proteome. On the other hand, in experimental mouse models there is probably less variation. We investigated the fecal protein content in mice to identify possible biomarkers and pathogenic mechanisms. METHODS: Fecal samples were collected at onset of inflammation in Galphai2-/- mice, a well-described spontaneous model of chronic colitis, and from healthy littermates...
2017: PloS One
https://www.readbyqxmd.com/read/28317204/cockroach-allergen-serine-proteinases-isolation-sequencing-and-signalling-via-proteinase-activated-receptor-2
#19
D J Polley, K Mihara, R Ramachandran, H Vliagoftis, B Renaux, M Saifeddine, M O Daines, S Boitano, M D Hollenberg
BACKGROUND: Allergy to the German cockroach (Blattella germanica) is a significant asthma risk factor for inner-city communities. Cockroach, like other allergens, contains trypsin-like enzyme activity that contributes to allergenicity and airway inflammation by activating proteinase-activated receptors (PARs). To date, the enzymes responsible for the proteolytic activity of German cockroach allergen have not been characterized. OBJECTIVES: We aimed to identify, isolate and characterize the trypsin-like proteinases in German cockroach allergen extracts used for clinical skin tests...
July 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28303089/protease-activated-receptor-2-par2-induces-long-term-depression-in-the-hippocampus-through-transient-receptor-potential-vanilloid-4-trpv4
#20
Efrat Shavit-Stein, Avital Artan-Furman, Ekaterina Feingold, Marina Ben Shimon, Zeev Itzekson-Hayosh, Joab Chapman, Andreas Vlachos, Nicola Maggio
Protease activated receptors (PARs) are involved in regulating synaptic transmission and plasticity in the brain. While it is well-accepted that PAR1 mediates long-term potentiation (LTP) of excitatory synaptic strength, the role of PAR2 in synaptic plasticity remains not well-understood. In this study, we assessed the role of PAR2-signaling in plasticity at hippocampal Schaffer collateral-CA1 synapses. Using field potential recordings, we report that PAR2-activation leads to long-term depression (LTD) of synaptic transmission through a protein kinase A -dependent, Transient Receptor Potential Vanilloid 4 -mediated mechanism, which requires the activation of N-methyl-D-aspartate receptors...
2017: Frontiers in Molecular Neuroscience
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