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Proteinase activated receptor

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https://www.readbyqxmd.com/read/29321953/matrix-metalloproteinase-1-facilitates-msc-migration-via-cleavage-of-igf-2-igfbp2-complex
#1
Shou P Guan, Alan T L Lam, Jennifer P Newman, Kevin L M Chua, Catherine Y L Kok, Siao T Chong, Melvin L K Chua, Paula Y P Lam
The specific mechanism underlying the tumor tropism of human mesenchymal stem cells (MSCs) for cancer is not well defined. We previously showed that the migration potential of MSCs correlated with the expression and protease activity of matrix metalloproteinase (MMP)-1. Furthermore, highly tumor-tropic MSCs expressed higher levels of MMP-1 and insulin-like growth factor (IGF)-2 than poorly migrating MSCs. In this study, we examined the functional roles of IGF-2 and MMP-1 in mediating the tumor tropism of MSCs...
January 2018: FEBS Open Bio
https://www.readbyqxmd.com/read/29295851/proteomic-profiling-for-cardiovascular-biomarker-discovery-in-orthostatic-hypotension
#2
Madeleine Johansson, Fabrizio Ricci, Nay Aung, Richard Sutton, Olle Melander, Artur Fedorowski
Orthostatic hypotension (OH) has been linked with higher incidence of cardiovascular disease, but little is known about the mechanisms behind this association. We aimed to identify cardiovascular disease biomarkers associated with OH through a proteomic profiling approach. Seven hundred seventy-eight patients with unexplained syncope or orthostatic intolerance underwent head-up tilt test and supine blood samples. Of these, 220 met diagnostic criteria of OH, and 179 demonstrated normal hemodynamic response during head-up tilt test...
January 2, 2018: Hypertension
https://www.readbyqxmd.com/read/29289470/prostanoid-dependent-bladder-pain-caused-by-proteinase-activated-receptor-2-activation-in-mice-involvement-of-trpv1-and-t-type-ca2-channels
#3
Maho Tsubota, Tomoka Ozaki, Yuko Hayashi, Yasumasa Okawa, Ayaka Fujimura, Fumiko Sekiguchi, Hiroyuki Nishikawa, Atsufumi Kawabata
We studied the pronociceptive role of proteinase-activated receptor-2 (PAR2) in mouse bladder. In female mice, intravesical infusion of the PAR2-activating peptide, SLIGRL-amide (SL), caused delayed mechanical hypersensitivity in the lower abdomen, namely 'referred hyperalgesia', 6-24 h after the administration. The PAR2-triggered referred hyperalgesia was prevented by indomethacin or a selective TRPV1 blocker, and restored by a T-type Ca2+ channel blocker. In human urothelial T24 cells, SL caused delayed prostaglandin E2 production and COX-2 upregulation...
December 15, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29285218/doxycycline-inhibits-breast-cancer-emt-and-metastasis-through-par-1-nf-%C3%AE%C2%BAb-mir-17-e-cadherin-pathway
#4
Weilong Zhong, Shuang Chen, Yuan Qin, Heng Zhang, Hongzhi Wang, Jing Meng, Longcong Huai, Qiang Zhang, Tingting Yin, Yueyang Lei, Jingxia Han, Lingfei He, Bo Sun, Huijuan Liu, Yanrong Liu, Honggang Zhou, Tao Sun, Cheng Yang
Doxycycline displays high efficiency for cancer therapy. However, the molecular mechanism is poorly understood. In our previous study, doxycycline was found to suppress tumor progression by directly targeting proteinase-activated receptor 1 (PAR1). In this study, microRNAs were found to be involved in PAR1-mediated anti-tumor effects of doxycycline. Among these miRNAs, miR-17 was found to promote breast cancer cell metastasis both in vivo and in vitro. Moreover, miR-17 could reverse partial doxycycline inhibition effects on breast cancer...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29261154/the-role-of-par2-in-tgf-%C3%AE-1-induced-erk-activation-and-cell-motility
#5
Hendrik Ungefroren, David Witte, Christian Fiedler, Thomas Gädeken, Roland Kaufmann, Hendrik Lehnert, Frank Gieseler, Bernhard H Rauch
BACKGROUND: Recently, the expression of proteinase-activated receptor 2 (PAR2) has been shown to be essential for activin receptor-like kinase 5 (ALK5)/SMAD-mediated signaling and cell migration by transforming growth factor (TGF)-β1. However, it is not known whether activation of non-SMAD TGF-β signaling (e.g., RAS-RAF-MEK-extracellular signal-regulated kinase (ERK) signaling) is required for cell migration and whether it is also dependent on PAR2. METHODS: RNA interference was used to deplete cells of PAR2, followed by xCELLigence technology to measure cell migration, phospho-immunoblotting to assess ERK1/2 activation, and co-immunoprecipitation to detect a PAR2-ALK5 physical interaction...
December 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29249975/fluoride-alters-klk4-expression-in-maturation-ameloblasts-through-androgen-and-progesterone-receptor-signaling
#6
Michael H Le, Yukiko Nakano, Dawud Abduweli Uyghurturk, Li Zhu, Pamela K Den Besten
Fluorosed maturation stage enamel is hypomineralized in part due to a delay in the removal of matrix proteins to inhibit final crystal growth. The delay in protein removal is likely related to reduced expression of kallikrein-related peptidase 4 (KLK4), resulting in a reduced matrix proteinase activity that found in fluorosed enamel. Klk4 transcription is known to be regulated in other cell types by androgen receptor (AR) and progesterone receptors (PR). In this study, we determined the possible role of fluoride in down-regulation of KLK4 expression through changes in AR and PR...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29235097/activation-of-astrocytic-par1-receptors-in-the-rat-nucleus-of-the-solitary-tract-regulates-breathing-through-modulation-of-presynaptic-trpv1
#7
Rafiq Huda, Zheng Chang, Jeehaeh Do, Donald R McCrimmon, Marco Martina
Many of the cellular and molecular mechanisms underlying astrocytic modulation of synaptic function remain poorly understood. Recent studies show that G-protein coupled receptor-mediated astrocyte activation modulates synaptic transmission in the nucleus of the solitary tract (NTS), a brainstem nucleus that regulates crucial physiological processes including cardiorespiratory activity. By using calcium imaging and patch clamp recordings in acute brain slices of wild-type and TRPV1-/- rats, we show that activation of proteinase-activated receptor 1 (PAR-1) in NTS astrocytes potentiates presynaptic glutamate release on NTS neurons...
December 12, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29230224/lipoarabinomannan-decreases-galectin-9-expression-and-tumor-necrosis-factor-pathway-in-macrophages-favoring-mycobacterium-tuberculosis-intracellular-growth
#8
Leslie Chávez-Galán, Lucero Ramon-Luing, Claudia Carranza, Irene Garcia, Isabel Sada-Ovalle
Lipoarabinomannan (LAM) is a lipid virulent factor secreted by Mycobacterium tuberculosis (Mtb). LAM can be found in the sputum and urine of patients with active tuberculosis. When human monocytes are differentiated into macrophages [monocyte-derived macrophages (MDM)] in the presence of LAM, MDM are poorly functional which may limit the immune response to Mtb infection. Our previous studies have shown that TIM3 and galectin (GAL)9 interaction induces anti-mycobacterial activity, and the expression levels of TIM3 and GAL9 are downregulated during Mtb infection...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29206862/recombinant-human-il-26-facilitates-the-innate-immune-response-to-endotoxin-in-the-bronchoalveolar-space-of-mice-in-vivo
#9
Aihua Bao, Karlhans Fru Che, Steven Bozinovski, Jie Ji, Joshua A Gregory, Susanna Kumlien Georén, Mikael Adner, Lars-Olaf Cardell, Anders Lindén
Interleukin (IL)-26 is released in response to bacterial endotoxin (LPS) in the bronchoalveolar space of humans in vivo and it may potentiate neutrophil chemotaxis by enhanced IL-26 receptor stimulation. However, the effects of extracellular IL-26 protein on the innate immune response in the lungs in vivo remain unknown. Here, we characterized these effects of IL-26 on a wide range of aspects of the innate immune response to LPS in different compartments of the lungs in vivo over time. We administrated recombinant human (rh) IL-26 protein in the bronchoalveolar space using intranasal instillation in a mouse in vivo model, with and without prior instillation of LPS...
2017: PloS One
https://www.readbyqxmd.com/read/29196708/the-serine-proteinase-hepsin-is-an-activator-of-pro-matrix-metalloproteinases-molecular-mechanisms-and-implications-for-extracellular-matrix-turnover
#10
David J Wilkinson, Antoine Desilets, Hua Lin, Sarah Charlton, Maria Del Carmen Arques, Adrian Falconer, Craig Bullock, Yu-Chen Hsu, Kristian Birchall, Alastair Hawkins, Paul Thompson, William R Ferrell, John Lockhart, Robin Plevin, Yadan Zhang, Emma Blain, Shu-Wha Lin, Richard Leduc, Jennifer M Milner, Andrew D Rowan
Increasing evidence implicates serine proteinases in the proteolytic cascades leading to the pathological destruction of extracellular matrices such as cartilage in osteoarthritis (OA). We have previously demonstrated that the type II transmembrane serine proteinase (TTSP) matriptase acts as a novel initiator of cartilage destruction via the induction and activation of matrix metalloproteinases (MMPs). Hepsin is another TTSP expressed in OA cartilage such that we hypothesized this proteinase may also contribute to matrix turnover...
December 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29195005/synthetic-indolactam-v-analogs-as-inhibitors-of-par2-induced-calcium-mobilization-in-triple-negative-breast-cancer-cells
#11
Jan Stein, Sonja Stahn, Jörg-Martin Neudörfl, Julia Sperlich, Hans-Günther Schmalz, Nicole Teusch
Human proteinase-activated receptor 2 (PAR2), a transmembrane G-Protein-coupled receptor (GPCR), represents an attractive target for a novel anti-cancer therapy as it plays a critical role in cell migration and invasion. Thus, selective PAR2 inhibitors possess a potential as anti-metastatic drugs. Knowing that the natural product teleocidin A2 is able to inhibit PAR2 in tumor cells, the goal of the present study was to elaborate structure-activity relationships and to identify potent PAR2 inhibitors with lower activity against the adverse target protein kinase C (PKC)...
December 1, 2017: ChemMedChem
https://www.readbyqxmd.com/read/29171721/heparan-sulfate-inhibits-inflammation-and-improves-wound-healing-through-down-regulating-nlrp3-inflammasome-in-diabetic-rats
#12
Tao Wang, Jun Zhao, Jian Zhang, Jiacai Mei, Mingzhe Shao, Ye Pan, Wenchao Yang, Yujie Jiang, Fang Liu, Weiping Jia
BACKGROUND: Heparan sulfate attenuated inflammatory response and improve diabetic wound healing in rats. However, the specific mechanisms that heparan sulfate suppresses inflammation are not clear. Nucleotide binding oligomerization domin-like receptor family pyrin domain containing-3 (NLRP3) is a major receptor involved in innate immune regulation. The present study aimed to elucidate the effect of heparan sulfate on NLRP3 and pro-inflammatory cytokines in diabetic wound. METHODS: Full-thickness wounds were created on the back of diabetic rats...
November 24, 2017: Journal of Diabetes
https://www.readbyqxmd.com/read/29165389/proteinase-activated-receptor-2-may-drive-cancer-progression-by-facilitating-tgf-%C3%AE-signaling
#13
REVIEW
Hendrik Ungefroren, David Witte, Bernhard H Rauch, Utz Settmacher, Hendrik Lehnert, Frank Gieseler, Roland Kaufmann
The G protein-coupled receptor proteinase-activated receptor 2 (PAR2) has been implicated in various aspects of cellular physiology including inflammation, obesity and cancer. In cancer, it usually acts as a driver of cancer progression in various tumor types by promoting invasion and metastasis in response to activation by serine proteinases. Recently, we discovered another mode through which PAR2 may enhance tumorigenesis: crosstalk with transforming growth factor-β (TGF-β) signaling to promote TGF-β1-induced cell migration/invasion and invasion-associated gene expression in ductal pancreatic adenocarcinoma (PDAC) cells...
November 22, 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
#14
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
#15
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/29105468/-effect-of-manual-acupuncture-electroacupuncture-and-moxibustion-on-intestinal-motility-and-expression-of-enteric-nervous-activity-related-proteins-in-functional-constipation-rats
#16
Xin Zhang, Xuan-Ping Zhang, Yu-Zhu Du, Hai-Jiao Xing, Rui Jia, Li-Jia Pan, Jing Xu, Chun-Sheng Jia
OBJECTIVE: To compare the effect of manual acupuncture (MA), electroacupuncture (EA) and moxibustion interventions on intestinal motility and expression of enteric nervous activity related proteins calcitonin gene related peptide (CGRP), transient receptor potential vanilloid 1 (TRPV 1) and proteinase activated receptor-4 (PAR-4) in colon tissue of rats with functional constipation (FC), so as to select a better intervention method for FC. METHODS: Sixty male SD rats were randomly divided into blank control (n=8), model (n=11), medication (n=8), MA (n=11), EA (n=11), and moxibustion (n=11) groups...
October 25, 2017: Zhen Ci Yan Jiu, Acupuncture Research
https://www.readbyqxmd.com/read/29097110/role-of-tumour-necrosis-factor-alpha-converting-enzyme-tace-adam17-and-associated-proteins-in-coronary-artery-disease-and-cardiac-events
#17
REVIEW
Melody Chemaly, Victoria McGilligan, Mark Gibson, Matthias Clauss, Steven Watterson, H Denis Alexander, Anthony John Bjourson, Aaron Peace
Tumour necrosis factor alpha converting enzyme (TACE/ADAM17) is a member of the A disintegrin and metalloproteinase (ADAM) family of ectodomain shedding proteinases. It regulates many inflammatory processes by cleaving several transmembrane proteins, including tumour necrosis factor alpha (TNFα) and its receptors tumour necrosis factor alpha receptor 1 and tumour necrosis factor alpha receptor 2. There is evidence that TACE is involved in several inflammatory diseases, such as ischaemia, heart failure, arthritis, atherosclerosis, diabetes and cancer as well as neurological and immune diseases...
October 30, 2017: Archives of Cardiovascular Diseases
https://www.readbyqxmd.com/read/28990808/microrna-205-mediates-proteinase-activated-receptor-2-par2-promoted-cancer-cell-migration
#18
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/28957707/label-free-visualization-and-quantification-of-single-cell-signaling-activity-using-metal-clad-waveguide-mcwg-based-microscopy
#19
Thomas Söllradl, Frederic A Banville, Ulrike Fröhlich, Michael Canva, Paul G Charette, Michel Grandbois
Label-free biosensing methods are very effective for studying cell signaling cascade activation induced by external stimuli. Assays generally involve a large number of cells and rely on the underlying assumption that cell response is homogeneous within a cell population. However, there is an increasing body of evidence showing that cell behavior may vary significantly even among genetically identical cells. In this paper, we demonstrate the use of metal-clad waveguide (MCWG)-based microscopy for label-free real-time monitoring of signaling activity and morphology changes in a small population of cells, with the ability to resolve individual cells...
September 18, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28940559/proteinase-activated-receptor-2-blockade-inhibits-changes-seen-in-a-chronic-murine-asthma-model
#20
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
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