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Proteinase activated receptor

Vivek Krishna Pulakazhi Venu, Mahmoud Saifeddine, Koichiro Mihara, Mahmoud El-Daly, Darrell Belke, Jonathan L E Dean, Edward R O'Brien, Simon A Hirota, Morley D Hollenberg
BACKGROUND AND PURPOSE: Previously, we demonstrated that exogenous Heat Shock Protein 27 (HSP27/gene, HSPB1) treatment of human endothelial progenitor cells (EPCs) increases the synthesis and secretion of VEGF, improves EPC-migration/re-endothelialization and decreases neo-intima formation, suggesting a role for HSPB1 in regulating EPC function. We hypothesized that HSPB1 could also affect mature endothelial cells (ECs) to alter EC-mediated vasoreactivity in vivo. Our work focused on eNOS/NO-dependent relaxation caused by acetylcholine and the coagulation pathway-activated receptor, proteinase-activated receptor-2 (PAR2)...
March 12, 2018: British Journal of Pharmacology
Darwin O Larco, Bradly M Bauman, Madelaine Cho-Clark, Shaila K Mani, T John Wu
Gonadotropin-releasing hormone (GnRH) neurons originate outside the central nervous system (CNS) in the nasal placode where their migration to the basal forebrain is dependent on the integration of multiple signaling cues during development. The proper migration and establishment of the GnRH neuronal population within the CNS are critical for normal pubertal onset and reproductive function. The endopeptidase EP24.15 is expressed along the migratory path of GnRH neurons and cleaves the full-length GnRH to generate the metabolite GnRH-(1-5)...
2018: Frontiers in Endocrinology
James Beattie, Hasanain Al-Khafaji, Pernille R Noer, Hanaa Esa Alkharobi, Aishah Alhodhodi, Josephine Meade, Reem El-Gendy, Claus Oxvig
The insulin-like growth factor (IGF) axis is required for the differentiation, development, and maintenance of bone tissue. Accordingly, dysregulation of this axis is associated with various skeletal pathologies including growth abnormalities and compromised bone structure. It is becoming increasingly apparent that the action of the IGF axis must be viewed holistically taking into account not just the actions of the growth factors and receptors, but also the influence of soluble high affinity IGF binding proteins (IGFBPs)...
2018: Frontiers in Endocrinology
Hui Liu, Yi Liu, Yi Li, Zhaoyun Liu, Liyan Li, Shaoxue Ding, Yihao Wang, Tian Zhang, Lijuan Li, Zonghong Shao, Rong Fu
Proteinase 3 (PR3) is released from neutrophils and regulates platelet activity, which is associated with cluster of differentiation (CD)177 antigen (NB1), a glycosylphosphatidylinositol-linked protein. In the present study, the effect of PR3 on thrombosis in paroxysmal nocturnal hemoglobinuria (PNH) and PNH-aplastic anemia (AA) syndrome was explored. The expression of PR3 and NB1 on CD59- neutrophils was detected by flow cytometry, immunofluorescence (IF), reverse transcription-quantitative polymerase chain reaction analysis and western blotting...
March 2018: Experimental and Therapeutic Medicine
Olivier Gouin, Killian L'Herondelle, Paul Buscaglia, Christelle Le Gall-Ianotto, Réginald Philippe, Nelig Legoux, Olivier Mignen, Virginie Buhé, Raphael Leschiera, Mehdi Sakka, Nathalie Kerfant, Jean-Luc Carré, Raphaele Le Garrec, Luc Lefeuvre, Nicolas Lebonvallet, Laurent Misery
Proteinase-activated receptor-2 (PAR-2) activation in basal keratinocytes stimulates inflammation via the Ca2+ -dependent production of mediators such as interleukin (IL)-1β, tumor necrosis factor (TNF)-α and thymic stromal lymphopoietin (TSLP). In this study, we investigated PAR-2 calcium signaling and the consequent production of inflammatory mediators in differentiated human primary keratinocytes (DhPKs). Stimulation with the PAR-2 activating peptide SLIGKV promoted Ca2+ store depletion in both undifferentiated human primary keratinocytes (UhPKs) and DhPKs...
February 16, 2018: Journal of Investigative Dermatology
Yang Cheng, Zhe Lin, Ju-Mei Wang, Long-Sheng Xing, Guang-Hua Xiong, Zhen Zou
C-type lectin (CTL) is usually considered as pattern recognition receptors in insect innate immunity. Here we found that CTL14 of Helicoverpa armigera was only activated in the fifth instar larvae not in the second instar by entomopathogen Beauveria bassiana infection. Recombinant CTL14 protein was found to form aggregates with zymosan and B. bassiana in vitro. Immunoprecipitation studies demonstrated that CTL14 interacted with serine proteinases (SP), serine proteinase inhibitor (serpin), prophenoloxidases (PPO) and vitellogenin (Vg) in the larval hemolymph...
February 14, 2018: Developmental and Comparative Immunology
Jared P Taylor, Melanie N Cash, Katherine E Santostefano, Mahito Nakanishi, Naohiro Terada, Mark A Wallet
The IFN-stimulated gene ubiquitin-specific proteinase 18 (USP18) encodes a protein that negatively regulates T1 IFN signaling via stearic inhibition of JAK1 recruitment to the IFN-α receptor 2 subunit (IFNAR2). Here, we demonstrate that USP18 expression is induced by HIV-1 in a T1 IFN-dependent manner. Experimental depletion of USP18 by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene editing results in a significant restriction of HIV-1 replication in an induced pluripotent stem cell (iPSC)-derived macrophage model...
February 13, 2018: Journal of Leukocyte Biology
Martin Steinhoff, Jörg Buddenkotte, Ethan A Lerner
To protect our body systems, there is a constant interactive conversation between the skin nervous and immune system. Important elements of this conversation in the skin include mast cells, basophils, and sensory nerve fibers. These cells employ a vast array of sensors that detect danger and react accordingly. This reaction, summarized as neurogenic inflammation, manifests at the conscious level as sensations including pain and itch. Here we provide a perspective on the blossoming knowledge that is illuminating connections between mast cells, basophils, and sensory nerve fibers in the mediation of itch...
March 2018: Immunological Reviews
Hui-Ying Tung, Evan Li, Cameron Landers, An Nguyen, Farrah Kheradmand, J Morgan Knight, David B Corry
Allergic asthma is a heterogeneous disorder that defies a unanimously acceptable definition, but is generally recognized through its highly characteristic clinical expression of dyspnea and cough accompanied by clinical data that document reversible or exaggerated airway constriction and obstruction. The generally rising prevalence of asthma in highly industrialized societies despite significant therapeutic advances suggests that the fundamental cause(s) of asthma remain poorly understood. Detailed analyses of both the indoor (built) and outdoor environments continue to support the concept that not only inhaled particulates, especially carbon-based particulate pollution, pollens, and fungal elements, but also many noxious gases and chemicals, especially biologically derived byproducts such as proteinases, are essential to asthma pathogenesis...
February 2018: Seminars in Respiratory and Critical Care Medicine
Abraham Neelankal John, Fang-Xu Jiang
One significant health issue that plagues contemporary society is that of Type 2 diabetes (T2D). This disease is characterised by higher-than-average blood glucose levels as a result of a combination of insulin resistance and insufficient insulin secretions from the β-cells of pancreatic islets of Langerhans. Previous developmental research into the pancreas has identified how early precursor genes of pancreatic β-cells, such as Cpal, Ngn3, NeuroD, Ptf1a, and cMyc, play an essential role in the differentiation of these cells...
December 14, 2017: Journal of Diabetes and its Complications
Xiao-Ping Huang, Xiao Wang, Xiao-Lan Xie, Gao-Ping Zhang, Feng-Jiao Lv, Wen-Ting Weng, Fei Qiu, Zhao-Fa Li, Jun-Sheng Lin, Yong Diao
Kallistatin is a unique serine proteinase inhibitor and heparin-binding protein. A previous study conducted by our group indicated that kallistatin has antiangiogenic and antitumoral activities. In the present study, we report that kallistatin specifically binds to membrane surface-expressed nucleolin with high affinity. Antibody-mediated neutralization or siRNA-induced nucleolin knockdown results in loss of kallistatin suppression of endothelial cell proliferation and migration in vitro and tumor angiogenesis and growth in vivo...
January 5, 2018: Oncotarget
Katerina Oikonomopoulou, Eleftherios P Diamandis, Morley D Hollenberg, Vinod Chandran
Proteinases are enzymes with established roles in physiological and pathological processes such as digestion and the homeostasis, destruction and repair of tissues. Over the past few years, the hormone-like properties of circulating proteinases have become increasingly appreciated. Some proteolytic enzymes trigger cell signalling via proteinase-activated receptors, a family of G protein-coupled receptors that have been implicated in inflammation and pain in inflammatory arthritis. Proteinases can also regulate ion flux owing to the cross-sensitization of transient receptor potential cation channel subfamily V members 1 and 4, which are associated with mechanosensing and pain...
February 8, 2018: Nature Reviews. Rheumatology
Hai-Yu Hu, Jia-Wei Ding, Ye-Qi Wu, Ya-Nan Xiang, Jian-Qiao Fang, Li-Hua Xuan, Jun-Ying Du, Jun-Fan Fang
OBJECTIVE: To observe the effect of electroacupuncture (EA) on mechanical hyperalgesia threshold (MHTs) and thermal hyperalgesia threshold (THTs) and content of proteinase-activated receptors 2 (PAR 2) in dorsal root ganglia (DRG) in rats with inflammatory pain, so as to explore its peripheral mechanism underlying improvement of inflammatory pain. METHODS: The present study contains two parts. 1) In the first part, 27 male SD rats were randomized into sham hyperalgesic priming (sham-HP) group and real hyperalgesic priming (HP) group (n=5 in the sham-HP group and n=6 in the HP group for the test of MHTs, n=8 in the two groups for the test of THTs)...
January 25, 2018: Zhen Ci Yan Jiu, Acupuncture Research
Kristoffer B Sugg, James F Markworth, Nathaniel P Disser, Andrew M Rizzi, Jeffrey R Talarek, Dylan C Sarver, Susan V Brooks, Christopher L Mendias
Platelet-derived growth factor receptor (PDGFR) signaling plays an important role in the fundamental biological activities of many cells that compose musculoskeletal tissues. However, little is known about the role of PDGFR signaling during tendon growth and remodeling in adult animals. Using the hindlimb synergist ablation model of tendon growth, our objectives were to determine the role of PDGFR signaling in the adaptation of tendons subjected to a mechanical growth stimulus, as well as to investigate the biological mechanisms behind this response...
December 13, 2017: American Journal of Physiology. Cell Physiology
Hamish A L Lemmey, Xi Ye, Hong Ding, Chris R Triggle, Christopher J Garland, Kim A Dora
Vascular dysfunction in small resistance arteries is observed during chronic elevations in blood glucose. Hyperglycaemia-associated effects on endothelium-dependent vasodilation have been well characterized, but effects on conducted vasodilation in the resistance vasculature are not known. Small mesenteric arteries were isolated from healthy and diabetic db/db mice, which were used as a model of chronic hyperglycaemia. Endothelium-dependent vasodilation via the Gq/11-coupled proteinase activated receptor 2 (PAR2) was stimulated with the selective agonist SLIGRL...
January 12, 2018: Vascular Pharmacology
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
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...
March 2018: Hypertension
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
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
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
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