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Proteinase activated receptor

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https://www.readbyqxmd.com/read/28931568/a-cross-talk-between-neuronal-urokinase-type-plasminogen-activator-upa-and-astrocytic-upa-receptor-upar-promotes-astrocytic-activation-and-synaptic-recovery-in-the-ischemic-brain
#1
Ariel Diaz, Paola Merino, Luis Guillermo Manrique, Juan Pablo Ospina, Lihong Cheng, Fang Wu, Valerie Jeanneret, Manuel Yepes
Urokinase-type plasminogen activator (uPA) is a serine proteinase that upon binding to its receptor (uPAR) catalyzes the conversion of plasminogen into plasmin on the cell surface. Our previous studies indicate that uPA and uPAR expression increase in the ischemic brain during the recovery phase from an acute ischemic injury, and that uPA binding to uPAR promotes neurological recovery following an acute ischemic stroke. Here we used male mice genetically deficient on either uPA (uPA(-/-)), or uPAR (uPAR(-/-)), or with a 4 amino acids substitution into the growth factor domain of uPA that abrogates its binding to uPAR (Plat(GFDhu/GFDhu)) to investigate the mechanism whereby uPA promotes neurorepair in the ischemic brain...
September 20, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28924232/infection-of-microglia-with-porphyromonas-gingivalis-promotes-cell-migration-and-an-inflammatory-response-through-the-gingipain-mediated-activation-of-protease-activated-receptor-2-in-mice
#2
Yicong Liu, Zhou Wu, Yurika Nakanishi, Junjun Ni, Yoshinori Hayashi, Fumiko Takayama, Yanmin Zhou, Tomoko Kadawaki, Hiroshi Nakanishi
Despite a clear correlation between periodontitis and cognitive decline in Alzheimer's disease, the precise mechanism underlying the relationship remains unclear. The periodontal pathogen Porphyromonas gingivalis produces a unique class of cysteine proteinases termed gingipains that comprises Arg-gingipain (Rgp) and Lys-gingipain (Kgp). Rgp and Kgp are important in the bacterial mediated host cell responses and the subsequent intracellular signaling in infected cells. In the present study, we attempted to clarify the potential effects of Rgp and Kgp on the cellular activation of brain-resident microglia...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28911149/insulin-like-growth-factor-bioactivity-stanniocalcin-2-pregnancy-associated-plasma-protein-a-and-igf-binding-protein-4-in-pleural-fluid-and-serum-from-patients-with-pulmonary-disease
#3
Ulrick Skipper Espelund, Mette Bjerre, Rikke Hjortebjerg, Torben Riis Rasmussen, Anders Lundby, Andreas Hoeflich, Birgitte Holst Folkersen, Claus Oxvig, Jan Frystyk
Context: Members of the insulin-like growth factor (IGF) system are primarily produced in the liver and secreted into the circulation, but they are also produced, recruited, and activated locally in tissues. Objective: To compare activity and concentrations of IGF system components in pleural fluid and blood. Design: Pathological pleural fluid, secondary to lung cancer or nonmalignant disease, and matching blood samples were collected from 24 patients ages 66...
September 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28842394/tgf-%C3%AE-1-alk5-mediated-cell-migration-is-dependent-on-the-protein-par2-but-not-on-par2-stimulated-gq-calcium-signaling
#4
Hendrik Ungefroren, David Witte, Koichiro Mihara, Bernhard H Rauch, Petra Henklein, Olaf Johren, 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 (Zeeh et al., 2016). Here, we show in the same cells that, conversely, the type I TGF-β; receptor ALK5 is dispensable for trypsin and PAR2 activating peptide (PAR2-AP)-induced migration...
August 25, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28835277/prophylactic-inhibition-of-neutrophil-elastase-prevents-the-development-of-chronic-neuropathic-pain-in-osteoarthritic-mice
#5
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/28804736/urokinase-type-plasminogen-activator-upa-and-its-receptor-upar-promote-neurorepair-in-the-ischemic-brain
#6
Paola Merino, Ariel Diaz, Manuel Yepes
Despite the fact that ischemic stroke has been considered a leading cause of mortality in the world, recent advances in our understanding of the pathophysiological mechanisms underlying the ischemic injury and the treatment of acute ischemic stroke patients have led to a sharp decrease in the number of stroke deaths. However, this decrease in stroke mortality has also led to an increase in the number of patients that survive the acute ischemic injury with different degrees of disability. Unfortunately, to this date we do not have an effective therapeutic strategy to promote neurological recovery in these growing population of stroke survivors...
2017: Receptors & Clinical Investigation
https://www.readbyqxmd.com/read/28771827/glucocorticoids-the-mode-of-action-in-bullous-pemphigoid
#7
REVIEW
Minna E Kubin, Lars Hellberg, Riitta Palatsi
Bullous pemphigoid (BP) is the most common of pemphigoid diseases caused by autoantibodies against the structures of dermoepidermal junction followed by complement activation, innate immune cell infiltration, neutrophil proteinase secretion and subepidermal blister formation. The first line treatment of BP is topical and systemic glucocorticoids (GC). Regulation of the immune system and inflammatory cells is the main target of GC actions. GCs act through genomic and non-genomic mechanisms. The human glucocorticoid receptor (GR) mediates most of the biologic effects of glucocorticoids: cytosolic GR binds GCs and is capable to bind to glucocorticoid response elements in DNA and either transactivate or transrepress genes depending on the tissue and cell-type...
August 3, 2017: Experimental Dermatology
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
#8
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/28754162/sensitization-of-asic3-by-proteinase-activated-receptor-2-signaling-contributes-to-acidosis-induced-nociception
#9
Jing Wu, Ting-Ting Liu, Yi-Mei Zhou, Chun-Yu Qiu, Ping Ren, Ming Jiao, Wang-Ping Hu
BACKGROUND: Tissue acidosis and inflammatory mediators play critical roles in pain. Pro-inflammatory agents trypsin and tryptase cleave and activate proteinase-activated receptor 2 (PAR2) expressed on sensory nerves, which is involved in peripheral mechanisms of inflammation and pain. Extracellular acidosis activates acid-sensing ion channel 3 (ASIC3) to trigger pain sensation. Here, we show that a functional interaction of PAR2 and ASIC3 could contribute to acidosis-induced nociception...
July 28, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28733353/use-of-proteomics-to-investigate-kidney-function-decline-over-5-years
#10
Axel C Carlsson, Erik Ingelsson, Johan Sundström, Juan Jesus Carrero, Stefan Gustafsson, Tobias Feldreich, Markus Stenemo, Anders Larsson, Lars Lind, Johan Ärnlöv
BACKGROUND AND OBJECTIVES: Using a discovery/replication approach, we investigated associations between a multiplex panel of 80 circulating proteins associated with cardiovascular pathology or inflammation, and eGFR decline per year and CKD incidence. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used two cohorts, the Prospective Investigation of the Vasculature in Uppsala Seniors Study (PIVUS; n=687, mean age of 70 years, 51% women) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n=360 men, mean age of 78 years), with 5-year follow-up data on eGFR...
July 21, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28691579/lipoxin-a4-suppresses-estrogen-induced-epithelial-mesenchymal-transition-via-alxr-dependent-manner-in-endometriosis
#11
Rong-Feng Wu, Zhi-Xiong Huang, Jing Ran, Song-Juan Dai, Dian-Chao Lin, Tai-Wei Ng, Qing-Xi Chen, Qiong-Hua Chen
OBJECTIVE: Epithelial-mesenchymal transition (EMT) is essential for embryogenesis, fibrosis, and tumor metastasis. Aberrant EMT phenomenon has been reported in endometriotic tissues of patients with endometriosis (EM). In this study, we further investigated the molecular mechanism of which lipoxin A4 (LXA4) suppresses estrogen (E2)-induced EMT in EM. STUDY DESIGN: The EMT markers were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot in eutopic endometrial epithelial cells (EECs) or investigated by immunohistochemistry and qRT-PCR in endometriotic lesion of EM mice...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28687195/%C3%AE-2-microglobulin-elicits-itch-related-responses-in-mice-through-the-direct-activation-of-primary-afferent-neurons-expressing-transient-receptor-potential-vanilloid-1
#12
Tsugunobu Andoh, Takahito Maki, Sikai Li, Daisuke Uta
Uremic pruritus is an unpleasant symptom in patients undergoing hemodialysis, and the underlying mechanisms remain unclear. β2-Microglobulin (β2-MG) is well-known as an MHC class I molecule and its level is increased in the plasma of patients undergoing hemodialysis. In this study, we investigated whether β2-MG was a pruritogen in mice. Intradermal injections of β2-MG into the rostral back induced scratching in a dose-dependent manner. Intradermal injection of β2-MG into the cheek also elicited scratching, but not wiping...
September 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28662718/thrombin-induced-tnfr-dependent-mir-181c-downregulation-promotes-mll1-and-nf-%C3%AE%C2%BAb-target-gene-expression-in-human-microglia
#13
Min Yin, Zhiying Chen, Yetong Ouyang, Huiyan Zhang, Zhigang Wan, Han Wang, Wei Wu, Xiaoping Yin
BACKGROUND: Controlling thrombin-driven microglial activation may serve as a therapeutic target for intracerebral hemorrhage (ICH). Here, we investigated microRNA (miRNA)-based regulation of thrombin-driven microglial activation using an in vitro thrombin toxicity model applied to primary human microglia. METHODS: A miRNA array identified 22 differential miRNA candidates. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) identified miR-181c as the most significantly downregulated miRNA...
June 29, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28643288/inhibitory-effect-of-fsllry-nh2-on-inflammatory-responses-induced-by-hydrogen-peroxide-in-hepg2-cells
#14
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/28631819/protective-effects-of-tannic-acid-on-pressure-overload-induced-cardiac-hypertrophy-and-underlying-mechanisms-in-rats
#15
Li Chu, Pinya Li, Tao Song, Xue Han, Xuan Zhang, Qiongtao Song, Tao Liu, Yuanyuan Zhang, Jianping Zhang
OBJECTIVES: The aim of this study was to examine the cardioprotective effects and latent mechanism of tannic acid (TA) on cardiac hypertrophy. METHODS: Abdominal aortic banding (AAB) was used to induce pressure overload-induced cardiac hypertrophy in male Wistar rats, sham-operated rats served as controls. AAB rats were treated with TA (20 and 40 mg/kg) or captoril. KEY FINDINGS: Abdominal aortic banding rats that received TA showed ameliorated pathological changes in cardiac morphology and coefficients, decreased cardiac hypertrophy and apoptosis, a reduction in over expressions of angiotensin type 1 receptor (AT1 R), angiotensin type 2 receptor (AT2 R), phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and transforming growth factor-β (TGF-β) mRNA, and modified expression of matrix metal proteinase-9 (MMP-9) mRNA in AAB rat hearts...
June 20, 2017: Journal of Pharmacy and Pharmacology
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
#16
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/28600123/multifunctional-and-redundant-roles-of-leptospira-interrogans-proteins-in-bacterial-adhesion-and-fibrin-clotting-inhibition
#17
Priscila R M Pereira, Luis G V Fernandes, Gisele O de Souza, Silvio A Vasconcellos, Marcos B Heinemann, Eliete C Romero, Ana L T O Nascimento
Pathogenic Leptopira is the etiological agent of leptospirosis, the most widespread zoonotic infection in the world. The disease represents a major public health problem, especially in tropical countries. The present work focused on two hypothetical proteins of unknown function, encoded by the genes LIC13059 and LIC10879, and predicted to be surface-exposed proteins. The genes were cloned and the proteins expressed using E. coli as a host system. We report that the recombinant proteins interacted with extracellular matrix (ECM) laminin, in a dose-dependent fashion and are novel potential adhesins...
May 31, 2017: International Journal of Medical Microbiology: IJMM
https://www.readbyqxmd.com/read/28586781/house-dust-mites-induce-production-of-endothelin-1-and-matrix-metalloproteinase-9-in-keratinocytes-via-proteinase-activated-receptor-2-activation
#18
Yoshihito Yamada, Tatsumi Matsumoto
BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by skin barrier dysfunction and abnormal immune response. House dust mites (HDM) are a major source of allergens, some of which have cysteine and serine protease activities. Keratinocytes stimulated by HDM-derived proteases have been suggested to contribute to the pathogenesis of AD by producing various cytokines. However, whether keratinocytes contribute to the induction of pruritus in AD, especially by producing pruritus-related mediators upon stimulation with HDM-derived proteases, has not been fully elucidated...
2017: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/28577299/upa-upar-system-activation-drives-a-glycolytic-phenotype-in-melanoma-cells
#19
Anna Laurenzana, Anastasia Chillà, Cristina Luciani, Silvia Peppicelli, Alessio Biagioni, Francesca Bianchini, Elena Tenedini, Eugenio Torre, Alessandra Mocali, Lido Calorini, Francesca Margheri, Gabriella Fibbi, Mario Del Rosso
In this manuscript, we show the involvement of the uPA/uPAR system in the regulation of aerobic glycolysis of melanoma cells. uPAR over-expression in human melanoma cells controls an invasive and glycolytic phenotype in normoxic conditions. uPAR down-regulation by siRNA or its uncoupling from integrins, and hence from integrin-linked tyrosine kinase receptors (IL-TKRs), by an antagonist peptide induced a striking inhibition of the PI3K/AKT/mTOR/HIF1α pathway, resulting into impairment of glucose uptake, decrease of several glycolytic enzymes and of PKM2, a checkpoint that controls metabolism of cancer cells...
June 2, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28546218/adamts5-deficiency-in-calcified-aortic-valves-is-associated-with-elevated-pro-osteogenic-activity-in-valvular-interstitial-cells
#20
Fei Li, Rui Song, Lihua Ao, T Brett Reece, Joseph C Cleveland, Nianguo Dong, David A Fullerton, Xianzhong Meng
OBJECTIVE: Extracellular matrix proteinases are implicated in the pathogenesis of calcific aortic valve disease. The ADAMTS5 (a disintegrin and metalloproteinase with thrombospondin motifs 5) enzyme is secreted, matrix-associated metalloendopeptidase, capable of degrading extracellular matrix proteins, particularly matrilin 2. We sought to determine the role of the ADAMTS5/matrilin 2 axis in mediating the phenotype transition of valvular interstitial cells (VICs) associated with calcific aortic valve disease...
July 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
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