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https://www.readbyqxmd.com/read/29148820/a-functional-kinase-short-interfering-ribonucleic-acid-screen-using-protease-activated-receptor-2-dependent-opening-of-transient-receptor-potential-vanilloid-4
#1
William G Darby, Megan S Grace, Kaylene J Simpson, Owen L Woodman, Peter McIntyre
Protease-activated receptor 2 (PAR2) is a proinflammatory G-protein coupled receptor (GPCR) that is activated by inflammatory proteases, and its activation initiates signaling pathways that modulate the nonselective cation channel transient receptor potential vanilloid-4 (TRPV4). PAR2-dependent opening of TRPV4 has been attributed to kinase activation, but the identity of the responsible enzymes is unknown. Deciphering the signaling pathways involved in the PAR2-dependent opening of TRPV4 may yield new targets for pain treatment...
November 17, 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/29140280/trpv3-channel-in-keratinocytes-in-scars-with-post-burn-pruritus
#2
Chun Wook Park, Hyun Ji Kim, Yong Won Choi, Bo Young Chung, So-Youn Woo, Dong-Keun Song, Hye One Kim
Post-burn pruritus is a common and distressing sequela of burn scars. Empirical antipruritic treatments usually fail to have a satisfactory outcome because of their limited selectivity and possible side effects. Therefore, novel drug targets need to be identified. Here, we aimed to investigate the possible role of protease-activated receptor 2 (PAR2) and transient receptor potential vanniloid 3 (TRPV3), along with the relation of TRPV3 to thymic stromal lymphopoietin (TSLP). Specimens from normal (unscarred) or burn-scarred (with or without pruritus) tissue were obtained from burn patients for this study...
November 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29131007/proteinase-activated-receptor-2-sensitivity-of-amplified-trpa1-activity-in-skeletal-muscle-afferent-nerves-and-exercise-pressor-reflex-in-rats-with-femoral-artery-occlusion
#3
Jihong Xing, Jianhua Li
BACKGROUND/AIMS: Limb ischemia occurs in peripheral artery disease (PAD). Sympathetic nerve activity (SNA) that regulates blood flow directed to the ischemic limb is exaggerated during exercise in this disease, and transient receptor potential channel A1 (TRPA1) in thin-fiber muscle afferents contributes to the amplified sympathetic response. The purpose of the present study was to determine the role of proteinase-activated receptor-2 (PAR2) in regulating abnormal TRPA1 function and the TRPA1-mediated sympathetic component of the exercise pressor reflex...
November 6, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29108655/proteinase-activated-receptor-2-distribution-and-expression-in-equine-small-intestine-tracts-following-herniation-through-the-epiploic-foramen
#4
Noemi Romagnoli, Augusta Zannoni, Chiara Bernardini, Thomas Gobbetti, Cristiano Bombardi, Anna Maria Rambaldi, Maria Morini, Francesco Dondi, Riccardo Rinnovati, Carlotta Lambertini, Alessandro Spadari
Proteinase-activated receptor 2 (PAR2) is a G-protein-coupled receptor for trypsin and mast cell tryptase; it is highly expressed at the intestinal level with multiple functions, such as epithelial permeability and intestinal motility. The aim of the study was to evaluate the distribution and expression of proteinase-activated receptor 2 in the small intestine during herniation through epiploic foramen. In this prospective clinical study, eight horses admitted for colic and which underwent exploratory laparotomy were considered...
October 31, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/29098568/the-signaling-of-protease-activated-receptor-2-activating-peptide-induced-contraction-in-cat-esophageal-smooth-muscle-cells
#5
Hyun Su Ha, Se Eun Lee, Hyun Seok Lee, Gil Hyung Kim, Chan Jong Yoon, Jong Soo Han, Ji-Yun Lee, Uy Dong Sohn
Protease-activated receptors (PARs) are a family of G protein-coupled receptors with a unique activation mechanism involving proteolytic cleavage of the extracellular N-terminal domain of the receptor. PAR2 has a contractile effect on esophageal smooth muscle. We investigate the signaling pathways of the PAR2-activating peptide (PAR2-AP) induced contraction in cat esophageal smooth muscle cells. The length of freshly isolated smooth muscle cells and permeabilized cells from feline esophagus were measured by scanning micrometry, and by confirming molecular basis via western blot analysis...
November 2, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/29047010/disrupted-cholinergic-modulation-can-underlie-abnormal-gamma-rhythms-in-schizophrenia-and-auditory-hallucination
#6
Jung Hoon Lee
The pathophysiology of auditory hallucination, a common symptom of schizophrenia, has yet been understood, but during auditory hallucination, primary auditory cortex (A1) shows paradoxical responses. When auditory stimuli are absent, A1 becomes hyperactive, while A1 responses to auditory stimuli are reduced. Such activation pattern of A1 responses during auditory hallucination is consistent with aberrant gamma rhythms in schizophrenia observed during auditory tasks, raising the possibility that the pathology underlying abnormal gamma rhythms can account for auditory hallucination...
October 18, 2017: Journal of Computational Neuroscience
https://www.readbyqxmd.com/read/29044292/investigation-of-the-filamin-a-dependent-mechanisms-of-tissue-factor-incorporation-into-microvesicles
#7
Mary Collier, Mary E W Collier, Camille Ettelaie, Benjamin T Goult, Anthony Maraveyas, Alison H Goodall
We have previously shown that phosphorylation of tissue factor (TF) at Ser253 increases the incorporation of TF into microvesicles (MVs) following protease-activated receptor 2 (PAR2) activation through a process involving filamin A, whereas phosphorylation of TF at Ser258 suppresses this process. Here, we examined the contribution of the individual phosphorylation of these serine residues to the interaction between filamin A and TF, and further examined how filamin A regulates the incorporation of TF into MVs...
October 10, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28990808/microrna-205-mediates-proteinase-activated-receptor-2-par2-promoted-cancer-cell-migration
#8
Xu Yang, Lan Yang, Yiming Ma, Xinhua Zhao, Hongying Wang
Activation of proteinase-activated receptor 2 (PAR2) promotes cell migration in cancers, but the exact mechanism underlying this process remains largely unknown. Here we report that activation of PAR2 reduced miR-205 expression, whereas inhibition of miR-205 promoted cell migration in cancer cells. Overexpression of miR-205 blocked PAR2-mediated stimulation of cell migration. BMPR1B was identified as a downstream target gene of miR-205. In colorectal carcinoma specimens from patients, the level of PAR2 was negatively correlated with that of miR-205, but it was positively associated with BMPR1B expression...
October 21, 2017: Cancer Investigation
https://www.readbyqxmd.com/read/28951199/a-t-cell-specific-knockout-reveals-an-important-role-for-protease-activated-receptor-2-in-lymphocyte-development
#9
Nidhish Francis, Alison L Every, Babatunde A Ayodele, Robert N Pike, Eleanor J Mackie, Charles N Pagel
Activation of protease-activated receptor-2 (PAR2) expressed by T cells has been linked to the bone loss associated with periodontitis. We generated PAR2 conditional-null mice and crossed these with mice expressing Cre recombinase under control of the Lck proximal promoter, to produce T cell-specific PAR2-null mice in order to further study the cellular mechanism involved in periodontitis. Here we report that efficient deletion of PAR2 in thymocytes isolated from T cell-specific PAR2-null mice resulted in thymic and splenic hypoplasia and a reduction in the cells of the cortex and a loss of distinction between the cortex and the medulla of the thymus...
September 22, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28943918/effects-of-silenced-par-2-on-cell-proliferation-invasion-and-metastasis-of-esophageal-cancer
#10
Jinmei Chen, Liqun Xie, Yanmin Zheng, Caihong Liu
The present study aimed to investigate the effect of protease-activated receptor 2 (PAR-2) on cell proliferation, invasion and metastasis in the esophageal EC109 cell line. Two short hairpin RNA (shRNA) expression plasmids were constructed based on the PAR-2 mRNA sequence in humans, and they were transfected into the EC109 esophageal cancer cell line, and the stable interference cell line (shRNA-PAR-2 EC109) was obtained by puromycin selection. Following transfection of PAR-2 shRNA-1, PAR-2 expression was significantly downregulated in mRNA level and protein level in EC109 cells (P<0...
October 2017: Oncology Letters
https://www.readbyqxmd.com/read/28940559/proteinase-activated-receptor-2-blockade-inhibits-changes-seen-in-a-chronic-murine-asthma-model
#11
M Asaduzzaman, C Davidson, D Nahirney, Y Fiteih, L Puttagunta, H Vliagoftis
BACKGROUND: Proteinase-Activated Receptor-2 (PAR2 ) is a G protein-coupled receptor activated by serine proteinases. We have shown that PAR2 activation in the airways is involved in the development of allergic inflammation and airway hyperresponsiveness (AHR) in acute murine models. We hypothesized that functional inhibition of PAR2 prevents allergic inflammation, AHR and airway remodeling in chronic allergic airway inflammation models. MATERIAL AND METHODS: We developed and used a 12 week model of cockroach extract (CE)-mediated AHR, airway inflammation and remodeling in BALB/c mice...
September 20, 2017: Allergy
https://www.readbyqxmd.com/read/28938620/pathological-expression-of-tissue-factor-confers-promising-antitumor-response-to-a-novel-therapeutic-antibody-sc1-in-triple-negative-breast-cancer-and-pancreatic-adenocarcinoma
#12
Xuesai Zhang, Qingrou Li, Hui Zhao, Lanping Ma, Tao Meng, Jianchang Qian, Rui Jin, Jingkang Shen, Ker Yu
The pathological presence of tissue factor (TF) in cancer cells promotes tumor-initiated thrombosis and cancer metastasis. We found that TF is aberrantly present in large percentage of aggressive triple negative breast cancer (TNBC) and pancreatic adenocarcinoma (PaC), two most lethal forms of malignancy that urgently need effective treatment. TF expression in TNBC clustered with higher levels of vimentin, basal-type keratins KRT5/14 and caveolin-1 but lower levels of luminal-type biomarkers. We developed a novel and specific anti-TF therapeutic antibody SC1, which displayed an exceedingly high potency against TF extracellular domain (EC50: 0...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28921694/protease-activated-receptor-2-controls-myelin-development-resiliency-and-repair
#13
Hyesook Yoon, Maja Radulovic, Grant Walters, Alex R Paulsen, Kristen Drucker, Phillip Starski, Jianmin Wu, David P Fairlie, Isobel A Scarisbrick
Oligodendrocytes are essential regulators of axonal energy homeostasis and electrical conduction and emerging target cells for restoration of neurological function. Here we investigate the role of protease activated receptor 2 (PAR2), a unique protease activated G protein-coupled receptor, in myelin development and repair using the spinal cord as a model. Results demonstrate that genetic deletion of PAR2 accelerates myelin production, including higher proteolipid protein (PLP) levels in the spinal cord at birth and higher levels of myelin basic protein and thickened myelin sheaths in adulthood...
December 2017: Glia
https://www.readbyqxmd.com/read/28881035/protease-activated-receptor-2-contributes-to-toxoplasma-gondii-mediated-gut-inflammation
#14
C Bonnart, G Feuillet, V Vasseur, N Cenac, N Vergnolle, N Blanchard
Toxoplasma gondii is a widespread intracellular parasite, which naturally enters the organism via the oral route and crosses the intestinal barrier to disseminate. In addition to neuronal and ocular pathologies, this pathogen also causes gut inflammation in a number of animals. This infection-triggered inflammation has been extensively studied in the C57BL/6 mice, highlighting the importance of the immune cells and their mediators in the development of gut pathology. However, despite their importance in inflammation, the role of protease-activated receptors (PAR) was never reported in the context of T...
November 2017: Parasite Immunology
https://www.readbyqxmd.com/read/28842394/transforming-growth-factor-%C3%AE-1-activin-receptor-like-kinase-5-mediated-cell-migration-is-dependent-on-the-protein-proteinase-activated-receptor-2-but-not-on-proteinase-activated-receptor-2-stimulated-gq-calcium-signaling
#15
Hendrik Ungefroren, David Witte, Koichiro Mihara, Bernhard H Rauch, Petra Henklein, Olaf Jöhren, Shirin Bonni, Utz Settmacher, Hendrik Lehnert, Morley D Hollenberg, Roland Kaufmann, Frank Gieseler
Transforming growth factor-β (TGF-β), serine proteinases such as trypsin, and proteinase-activated receptor 2 (PAR2) promote tumor development by stimulating invasion and metastasis. Previously, we found that in cancer cells derived from pancreatic ductal adenocarcinoma (PDAC) PAR2 protein is necessary for TGF-β1-dependent cell motility. Here, we show in the same cells that, conversely, the type I TGF-β receptor activin receptor-like kinase 5 is dispensable for trypsin and PAR2 activating peptide (PAR2-AP)-induced migration...
November 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28835277/prophylactic-inhibition-of-neutrophil-elastase-prevents-the-development-of-chronic-neuropathic-pain-in-osteoarthritic-mice
#16
Milind M Muley, Eugene Krustev, Allison R Reid, Jason J McDougall
BACKGROUND: A subset of osteoarthritis (OA) patients experience joint pain with neuropathic characteristics. Mediators such as neutrophil elastase, a serine proteinase, may be released during acute OA inflammatory flares. We have previously shown that local administration of neutrophil elastase causes joint inflammation and pain via activation of proteinase-activated receptor-2 (PAR2). The aim of this study was to examine the contribution of endogenous neutrophil elastase and PAR2 to the development of joint inflammation, pain, and neuropathy associated with monoiodoacetate (MIA)-induced experimental OA...
August 23, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28827518/activated-protein-c-protects-from-gvhd-via-par2-par3-signalling-in-regulatory-t-cells
#17
Satish Ranjan, Alexander Goihl, Shrey Kohli, Ihsan Gadi, Mandy Pierau, Khurrum Shahzad, Dheerendra Gupta, Fabian Bock, Hongjie Wang, Haroon Shaikh, Thilo Kähne, Dirk Reinhold, Ute Bank, Ana C Zenclussen, Jana Niemz, Tina M Schnöder, Monika Brunner-Weinzierl, Thomas Fischer, Thomas Kalinski, Burkhart Schraven, Thomas Luft, Jochen Huehn, Michael Naumann, Florian H Heidel, Berend Isermann
Graft-vs.-host disease (GvHD) is a major complication of allogenic hematopoietic stem-cell(HSC) transplantation. GvHD is associated with loss of endothelial thrombomodulin, but the relevance of this for the adaptive immune response to transplanted HSCs remains unknown. Here we show that the protease-activated protein C (aPC), which is generated by thrombomodulin, ameliorates GvHD aPC restricts allogenic T-cell activation via the protease activated receptor (PAR)2/PAR3 heterodimer on regulatory T-cells (Tregs, CD4(+)FOXP3(+))...
August 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28797985/the-role-and-mechanism-of-cathepsin-g-in-dermatomyositis
#18
Siming Gao, Honglin Zhu, Huan Yang, Huali Zhang, Qiuxiang Li, Hui Luo
Dermatomyositis (DM) is an idiopathic inflammatory myopathy characterized by CD4+ T cells and B cells infiltration in perivascular and muscle tissue. Although the infiltration of inflammatory cells plays a key role in muscle damage, the exact mechanism is not clear. Cathepsin G (CTSG) is a member of the serine proteases family and can increase the permeability of vascular endothelial cells and the chemotaxis of inflammatory cells. In this study, we found that the expression of CTSG was increased in peripheral blood mononuclear cells and muscle tissues of DM patients...
October 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28769800/cathepsin-s-is-involved-in-th17-differentiation-through-the-upregulation-of-il-6-by-activating-par-2-after-systemic-exposure-to-lipopolysaccharide-from-porphyromonas-gingivalis
#19
Masato Dekita, Zhou Wu, Junjun Ni, Xinwen Zhang, Yicong Liu, Xu Yan, Hiroshi Nakanishi, Ichiro Takahashi
Positive links have been found between periodontitis and numerous diseases in humans via persistent inflammation throughout the body. However, the main factors responsible for maintaining this pro-inflammatory condition are poorly understood. The spleen, the largest secondary immune organ, is a central hub regulating the immune response/inflammation due to the dendritic cell (DC) response to CD4(+) T cell subtype differentiation, and lysosomal proteinase cathepsin S (CatS) is known to be involved in DC functions...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28768771/activation-of-mas-related-g-protein-coupled-receptors-by-the-house-dust-mite-cysteine-protease-der-p1-provides-a-new-mechanism-linking-allergy-and-inflammation
#20
Vemuri B Reddy, Ethan A Lerner
Cysteine and serine proteases function via protease-activated and mas-related G-protein-coupled receptors (Mrgprs) to contribute to allergy and inflammation. Der p1 is a cysteine protease and major allergen from the house dust mite and is associated with allergic rhinitis and allergic asthma. Der p1 activates protease-activated receptor 2 and induces the release of the pro-inflammatory cytokine IL-6 from cells. However, the possibility that Der p1 acts on Mrgprs has not been considered. We report here that ratiometric calcium imaging reveals that Der p1 activates the human receptor MRGPRX1 and the mouse homolog MrgprC11, implicated previously in itch...
October 20, 2017: Journal of Biological Chemistry
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