keyword
MENU ▼
Read by QxMD icon Read
search

Protease activated receptor 2

keyword
https://www.readbyqxmd.com/read/29348072/structure-based-development-of-an-osteoprotegerin-like-glycopeptide-that-blocks-rankl-rank-interactions-and-reduces-ovariectomy-induced-bone-loss-in-mice
#1
Chao Liu, Xiao Chen, Xin Zhi, Weizong Weng, Quan Li, Xiang Li, Yan Zou, Jiacan Su, Hong-Gang Hu
Osteoporosis is a metabolic bone disease characterized by low bone mass and micro-architectural deterioration of bone, for which the underlying mechanism is an imbalance between bone resorption and bone remodeling. The protein-protein interactions between receptor activator of nuclear factor-κB ligand (RANKL), RANK (its receptor), and osteoprotegerin (OPG), are known to mediate the development and activation of osteoclasts in bone remodeling, and are regarded as a pivotal therapeutic target for the treatment of osteoporosis...
January 10, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29345066/protease-activated-receptor-2-is-necessary-for-neutrophil-chemorepulsion-induced-by-trypsin-tryptase-or-dipeptidyl-peptidase-iv
#2
Michael J V White, Luis E Chinea, Darrell Pilling, Richard H Gomer
Compared to neutrophil chemoattractants, relatively little is known about the mechanism neutrophils use to respond to chemorepellents. We previously found that the soluble extracellular protein dipeptidyl peptidase IV (DPPIV) is a neutrophil chemorepellent. In this report, we show that an inhibitor of the protease activated receptor 2 (PAR2) blocks DPPIV-induced human neutrophil chemorepulsion, and that PAR2 agonists such as trypsin, tryptase, 2f-LIGRL, SLIGKV, and AC55541 induce human neutrophil chemorepulsion...
January 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29334656/activated-protein-c-suppresses-osteoclast-differentiation-via-endothelial-protein-c-receptor-protease-activated-receptor-1-sphingosine-1-phosphate-receptor-and-apolipoprotein-e-receptor-2
#3
Kakunoshin Yoshida, Nobuyuki Akita, Takayuki Okamoto, Kunihiro Asanuma, Atsumasa Uchida, Akihiro Sudo, Motomu Shimaoka, Koji Suzuki, Tatsuya Hayashi
INTRODUCTION: Bone remodeling relies on a delicate balance between formation and resorption of bone tissues, processes in which bone-forming osteoblasts and bone-resorbing osteoclasts play central roles. Recently, we reported that anticoagulant activated protein C (APC) promotes osteoblast proliferation, but the role of the blood coagulation system in bone remodeling remains unclear. In this study, to further elucidate the relationship between bone remodeling and blood coagulation, we investigated the effect of APC on osteoclast differentiation...
January 3, 2018: Thrombosis Research
https://www.readbyqxmd.com/read/29332129/aspergillus-fumigatus-increased-par-2-expression-and-elevated-proinflammatory-cytokines-expression-through-the-pathway-of-par-2-erk1-2-in-cornea
#4
Yawen Niu, Guiqiu Zhao, Cui Li, Jing Lin, Nan Jiang, Chengye Che, Jie Zhang, Qiang Xu
Purpose: To determine the role of protease-activated receptor-2 (PAR-2) in cornea infected by Aspergillus fumigatus. Methods: PAR-2 was tested in normal and infected corneas of C57BL/6 mice. Mice corneas were infected with A. fumigatus with or without pretreatment of PAR-2 antagonist (FSLLRY-NH2). Polymorphonuclear neutrophilic leukocytes (PMNs) were stimulated with 75% ethanol-killed A. fumigatus with or without pretreatment of FSLLRY-NH2. Disease severity was documented by clinical score and photographs with a slit lamp...
January 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29325127/inhibiting-trophoblast-par-1-overexpression-suppresses-sflt-1-induced-anti-angiogenesis-and-abnormal-vascular-remodeling-a-possible-therapeutic-approach-for-preeclampsia
#5
Yin Zhao, YanFang Zheng, XiaoXia Liu, QingQing Luo, Di Wu, XiaoPing Liu, Li Zou
STUDY QUESTION: Is it possible to improve vascular remodeling by inhibiting the excessive expression of protease activated receptor 1 (PAR-1) in trophoblast of abnormal placenta? SUMMARY ANSWER: Inhibition of trophoblast PAR-1 overexpression may promote placental angiogenesis and vascular remodeling, offering an alternative therapeutic approach for preeclampsia. WHAT IS KNOWN ALREADY: PAR-1 is high-affinity receptor of thrombin. Thrombin increases sFlt-1 secretion in trophoblast via the activation of PAR-1...
January 9, 2018: Molecular Human Reproduction
https://www.readbyqxmd.com/read/29321953/matrix-metalloproteinase-1-facilitates-msc-migration-via-cleavage-of-igf-2-igfbp2-complex
#6
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/29318541/biotin-chasing-assay-to-evaluate-upar-stability-and-cleavage-on-the%C3%A2-surface-of-cells
#7
Vladimir Leksa, Herbert B Schiller, Hannes Stockinger
The plasminogen activation system, i.e., the fibrinolytic system, is one of the major plasma proteolytic pathways. The proteolytic conversion of the zymogen plasminogen to the active serine protease plasmin is on the cell surface catalyzed by the serine protease urokinase-type plasminogen activator (urokinase, uPA). Upon binding to the urokinase receptor (uPAR, CD87), single-chain pro-uPA is processed to double-chain uPA which in turn specifically converts cell-bound plasminogen to plasmin. Plasmin is harnessed in many physiological processes, e...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29316408/agonists-and-antagonists-of-protease-activated-receptor-2-discovered-within-a-dna-encoded-chemical-library-using-mutational-stabilization-of-the-target
#8
Dean G Brown, Giles A Brown, Paolo Centrella, Kaan Certel, Robert M Cooke, John W Cuozzo, Niek Dekker, Christoph E Dumelin, Andrew Ferguson, Cédric Fiez-Vandal, Stefan Geschwindner, Marie-Aude Guié, Sevan Habeshian, Anthony D Keefe, Oliver Schlenker, Eric A Sigel, Arjan Snijder, Holly T Soutter, Linda Sundström, Dawn M Troast, Giselle Wiggins, Jing Zhang, Ying Zhang, Matthew A Clark
The discovery of ligands via affinity-mediated selection of DNA-encoded chemical libraries is driven by the quality and concentration of the protein target. G-protein-coupled receptors (GPCRs) and other membrane-bound targets can be difficult to isolate in their functional state and at high concentrations, and therefore have been challenging for affinity-mediated selection. Here, we report a successful selection campaign against protease-activated receptor 2 (PAR2). Using a thermo-stabilized mutant of PAR2, we conducted affinity selection using our >100-billion-compound DNA-encoded library...
January 1, 2018: SLAS Discovery
https://www.readbyqxmd.com/read/29312598/interleukin-22-participates-in-the-inflammatory-process-of-vitiligo
#9
Jinjin Dong, Xiaohong An, Hui Zhong, Yichuan Wang, Jing Shang, Jia Zhou
Vitiligo is an acquired depigmentary skin inflammatory disorder. The pathogenesis of inflammatory skin disease involves the release of cytokines from keratinocytes, including interleukin (IL)-1β. IL-22 belongs to a family of cytokines structurally related to IL-10, including IL-19, IL-20, IL-24, and IL-26. In contrast to IL-10, IL-22 has proinflammatory activities. Among skin cell populations only keratinocytes are the major targets of IL-22. In the present study, we demonstrated that IL-22 promoting IL-1β secretion from keratinocytes via the Reactive oxygen species (ROS)-NOD-like receptor family, pyrin domain containing 3 (NLRP3)-caspase-1 pathway...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29301867/protease-signaling-regulates-apical-cell-extrusion-cell-contacts-and-proliferation-in-epithelia
#10
Antonino Schepis, Adrian Barker, Yoga Srinivasan, Eaman Balouch, Yaowu Zheng, Ian Lam, Hilary Clay, Chung-Der Hsiao, Shaun R Coughlin
Mechanisms that sense and regulate epithelial morphogenesis, integrity, and homeostasis are incompletely understood. Protease-activated receptor 2 (Par2), the Par2-activating membrane-tethered protease matriptase, and its inhibitor, hepatocyte activator inhibitor 1 (Hai1), are coexpressed in most epithelia and may make up a local signaling system that regulates epithelial behavior. We explored the role of Par2b in matriptase-dependent skin abnormalities in Hai1a-deficient zebrafish embryos. We show an unexpected role for Par2b in regulation of epithelial apical cell extrusion, roles in regulating proliferation that were opposite in distinct but adjacent epithelial monolayers, and roles in regulating cell-cell junctions, mobility, survival, and expression of genes involved in tissue remodeling and inflammation...
January 4, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29288468/interactions-between-bradykinin-and-plasmin-in-the-endothelial-ca2-response
#11
Yukako Obata, Kazuhiko Takeuchi, Jiazhang Wei, Akio Hakamata, Keiichi Odagiri, Yoshiki Nakajima, Hiroshi Watanabe
Plasmin is a fibrinolytic factor and a serine protease that activates protease-activated receptors (PARs) to produce endothelium-derived relaxing factors such as nitric oxide and prostacyclin. Nitric oxide and prostacyclin production is regulated, at least in part, by the intracellular Ca2+ concentration in various blood vessel types. Bradykinin and plasmin stimulate vascular endothelial cells and work simultaneously in pathophysiological conditions such as thrombosis and inflammation. Here, we explored the interactions between bradykinin and plasmin in the endothelial Ca2+ response using the fluorescent indicator, Fura-2/AM, in primary cultures of porcine aortic endothelial cells (PAECs)...
December 29, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29285303/insulin-receptor-substrate-4-interacts-with-ubiquitin-specific-protease-18-to-activate-the-jak-stat-signaling-pathway
#12
Baihai Jiao, Xuezhen Shi, Yanzhao Chen, Haiyan Ye, Min Yao, Wenxu Hong, Shilin Li, Xiaoqiong Duan, Yujia Li, Yancui Wang, Limin Chen
Ubiquitin-specific protease 18 (USP18) as a negative regulator of the Jak/STAT signaling pathway plays an important role in the host innate immune response. USP18 has been shown to bind to the type I interferon receptor subunit 2 (IFNAR2) to down-regulate the Jak/STAT signaling. In this study, we showed that insulin receptor substrate (IRS)-4 functioned as a novel USP18-binding protein. Co-precipitation assays revealed that two regions (amino acids 335-400 and 1094-1257) of IRS4 were related to bind to the C- terminal region of USP18...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29250115/thrombin-induced-calpain-activation-promotes-protease-activated-receptor-1-internalization
#13
Alejandro Alvarez-Arce, Irene Lee-Rivera, Edith López, Arturo Hernández-Cruz, Ana María López-Colomé
The serine protease thrombin activates Protease-Activated Receptors (PARs), a family of G-protein-coupled receptors (GPCRs) activated by the proteolytic cleavage of their extracellular N-terminal domain. Four members of this family have been identified: PAR1-4. The activation of Protease-Activated Receptor 1(PAR1), the prototype of this receptor family, leads to an increase in intracellular Ca+2 concentration ([Ca+2]i) mediated by Gq11α coupling and phospholipase C (PLC) activation. We have previously shown that the stimulation of PAR1 by thrombin promotes intracellular signaling leading to RPE cell transformation, proliferation, and migration which characterize fibroproliferative eye diseases leading to blindness...
2017: International Journal of Cell Biology
https://www.readbyqxmd.com/read/29247993/interleukin-33-il-33-a-nuclear-cytokine-from-the-il-1-family
#14
REVIEW
Corinne Cayrol, Jean-Philippe Girard
Interleukin-33 (IL-33) is a tissue-derived nuclear cytokine from the IL-1 family abundantly expressed in endothelial cells, epithelial cells and fibroblast-like cells, both during homeostasis and inflammation. It functions as an alarm signal (alarmin) released upon cell injury or tissue damage to alert immune cells expressing the ST2 receptor (IL-1RL1). The major targets of IL-33 in vivo are tissue-resident immune cells such as mast cells, group 2 innate lymphoid cells (ILC2s) and regulatory T cells (Tregs)...
January 2018: Immunological Reviews
https://www.readbyqxmd.com/read/29246902/identification-of-the-coagulation-factor-viia-integrin-binding-site-required-for-pro-angiogenic-par2-signaling
#15
Andrea S Rothmeier, Enbo Liu, Sagarika Chakrabarty, Jennifer Disse, Barbara M Mueller, Henrik Østergaard, Wolfram Ruf
The tissue factor (TF) pathway serves both hemostasis and cell signaling, but how cells control these divergent functions of TF remains incompletely understood. TF is the receptor and scaffold of coagulation proteases cleaving protease activated receptor (PAR) 2 that plays pivotal roles in angiogenesis and tumor development. Here we demonstrate that coagulation factor (F) VIIa elicits TF cytoplasmic domain-dependent pro-angiogenic cell signaling independent of the alternative PAR2 activator matriptase. We identify a Lys-Gly-Glu (KGE) integrin binding motif in the FVIIa protease domain that is required for association of the TF-FVIIa complex with the active conformer of integrin β1...
December 15, 2017: Blood
https://www.readbyqxmd.com/read/29240923/neutrophil-activation-signature-in-juvenile-idiopathic-arthritis-indicates-the-presence-of-low-density-granulocytes
#16
Kavitha Ramanathan, Anna Glaser, Hanna Lythgoe, Joanne Ong, Michael W Beresford, Angela Midgley, Helen L Wright
Objective: JIA is an autoimmune, inflammatory disease with involvement of innate and adaptive immune responses. However, the role of neutrophils in JIA pathogenesis remains unclear. This study aimed to identify and validate neutrophil gene expression signatures in JIA using public microarray datasets and new clinical samples. Methods: Three suitable datasets were analysed by significance analysis of microarray and Ingenuity. Neutrophils and peripheral blood mononuclear cells (PBMCs) were isolated from a new cohort of JIA patients and healthy paediatric controls (HCs)...
December 12, 2017: Rheumatology
https://www.readbyqxmd.com/read/29228131/synaptic-potentiation-at-basal-and-apical-dendrites-of-hippocampal-pyramidal-neurons-involves-activation-of-a-distinct-set-of-extracellular-and-intracellular-molecular-cues
#17
Patrycja Brzdak, Olga Wójcicka, Monika Zareba-Koziol, Daniel Minge, Christian Henneberger, Jakub Wlodarczyk, Jerzy W Mozrzymas, Tomasz Wójtowicz
In the central nervous system, several forms of experience-dependent plasticity, learning and memory require the activity-dependent control of synaptic efficacy. Despite substantial progress in describing synaptic plasticity, mechanisms related to heterogeneity of synaptic functions at local circuits remain elusive. Here we studied the functional and molecular aspects of hippocampal circuit plasticity by analyzing excitatory synapses at basal and apical dendrites of mouse hippocampal pyramidal cells (CA1 region) in acute brain slices...
December 8, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/29228045/mycobacterial-infection-induces-higher-interleukin-1%C3%AE-and-dysregulated-lung-inflammation-in-mice-with-defective-leukocyte-nadph-oxidase
#18
Wen-Cheng Chao, Chia-Liang Yen, Cheng-Yuan Hsieh, Ya-Fang Huang, Yau-Lin Tseng, Peter Andrija Nigrovic, Chi-Chang Shieh
Granulomatous inflammation causes severe tissue damage in mycobacterial infection while redox status was reported to be crucial in the granulomatous inflammation. Here, we used a NADPH oxidase 2 (NOX2)-deficient mice (Ncf1-/-) to investigate the role of leukocyte-produced reactive oxygen species (ROS) in mycobacterium-induced granulomatous inflammation. We found poorly controlled mycobacterial proliferation, significant body weight loss, and a high mortality rate after M. marinum infection in Ncf1-/- mice. Moreover, we noticed loose and neutrophilic granulomas and higher levels of interleukin (IL)-1β and neutrophil chemokines in Ncf1-/- mice when compared with those in wild type mice...
2017: PloS One
https://www.readbyqxmd.com/read/29221590/activit%C3%A3-s-immunomodulatrice-anti-inflammatoire-antiprurigineuse-et-tol%C3%A3-rog%C3%A3-nique-induites-par-i-modulia%C3%A2-un-extrait-issu-de-culture-d%C3%A2-aquaphilus-dolomiae-dans-les-mod%C3%A3-les-pharmacologiques-de-dermatite-atopique-immunomodulatory-anti-inflammatory-anti-pruritus
#19
T Nguyen, N Castex-Rizzi, D Redoulès
Atopic dermatitis (AD) is an inflammatory and pruritic dermatosis of multifactorial origin. Topical steroids are the first line treatment for severe AD however alternatives treatment are increasingly needed. A biological concentrate was elaborated from culture of an Avène aquatic microflora isolate namely Aquaphilus dolomiae. Numerous extracts were evaluated in relevant AD in vitro models with human keratinocytes. Among these extracts, a particular one I-modulia® was found to be remarkable in terms of pharmacological activities: innate immunity modulating by agonizing Toll like receptor (TLR)2, TLR4 and TLR5, induction of anti-microbial peptides, inhibition of cytokines characteristics of T helper (Th)1, Th2 and Th17 responses, inhibition of Protease-activated-receptor (PAR) 2 and Thymic-stromal-lymphopoeitin (TSLP) both being known to be upregulated in pruritus...
January 2017: Annales de Dermatologie et de Vénéréologie
https://www.readbyqxmd.com/read/29215065/toll-like-receptor-activation-induces-degeneration-of-human-intervertebral-discs
#20
Emerson Krock, Derek H Rosenzweig, J Brooke Currie, Daniel G Bisson, Jean A Ouellet, Lisbet Haglund
Toll-like receptors (TLR) are activated by endogenous alarmins such as fragmented extracellular matrix compounds found in the degenerating disc. TLRs regulate cytokine, neurotrophin, and protease expression in human disc cells in vitro, and thus control key factors in disc degeneration. However, whether TLR activation leads to degenerative changes in intact human discs is unclear. Nucleus pulposus (NP) cells isolated from non-degenerating discs increase IL-1β and nerve growth factor gene expression following treatment with Pam2CSK4 (TLR2/6 agonist) but not Pam3CSK4 (TLR1/2 agonist)...
December 7, 2017: Scientific Reports
keyword
keyword
77545
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"