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Thrombospondin

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https://www.readbyqxmd.com/read/29146705/complement-c3-is-a-novel-modulator-of-the-anti-fviii-immune-response
#1
Julie Rayes, Mathieu Ing, Sandrine Delignat, Ivan Peyron, Laurent Gilardin, Carl-Wilhelm Vogel, David C Fritzinger, Véronique Frémeaux-Bacchi, Srinivas V Kaveri, Lubka T Roumenina, Sébastien Lacroix-Desmazes
Development of neutralizing antibodies against therapeutic factor VIII (FVIII) is the most serious complication of the treatment of hemophilia A. Increasing evidence shows the multifactorial origin of the anti-FVIII immune response, combining both genetic and environmental factors. While a role for the complement system on innate as well as adaptive immunity has been documented, the implication of complement activation on the onset of the anti-FVIII immune response is unknown. Here, using in vitro assays for FVIII endocytosis by human monocyte-derived dendritic cells and presentation to T cells, as well as animal models of in vivo complement depletion, we show a novel role for complement C3 in enhancing the immune response against therapeutic FVIII...
November 16, 2017: Haematologica
https://www.readbyqxmd.com/read/29138320/structural-basis-for-antibody-recognition-of-the-nanp-repeats-in-plasmodium-falciparum-circumsporozoite-protein
#2
David Oyen, Jonathan L Torres, Ulrike Wille-Reece, Christian F Ockenhouse, Daniel Emerling, Jacob Glanville, Wayne Volkmuth, Yevel Flores-Garcia, Fidel Zavala, Andrew B Ward, C Richter King, Ian A Wilson
Acquired resistance against antimalarial drugs has further increased the need for an effective malaria vaccine. The current leading candidate, RTS,S, is a recombinant circumsporozoite protein (CSP)-based vaccine against Plasmodium falciparum that contains 19 NANP repeats followed by a thrombospondin repeat domain. Although RTS,S has undergone extensive clinical testing and has progressed through phase III clinical trials, continued efforts are underway to enhance its efficacy and duration of protection. Here, we determined that two monoclonal antibodies (mAbs 311 and 317), isolated from a recent controlled human malaria infection trial exploring a delayed fractional dose, inhibit parasite development in vivo by at least 97%...
November 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29138119/thrombospondin-4-in-tissue-remodeling
#3
REVIEW
Olga Stenina-Adognravi, Edward F Plow
Thrombospondin-4 (TSP-4) belongs to the thrombospondin protein family that consists of five highly homologous members. A number of novel functions have been recently assigned to TSP-4 in cardiovascular and nervous systems, inflammation, cancer, and the motor unit, which have attracted attention to this extracellular matrix (ECM) protein. These newly discovered functions set TSP-4 apart from other thrombospondins. For example, TSP-4 promotes angiogenesis while other TSPs either prevent it or have no effect on new blood vessel growth; TSP-4 reduces fibrosis and collagen production while TSP-1 and TSP-2 promote fibrosis in several organs; unlike other TSPs, TSP-4 appears to have some structural functions in ECM...
November 11, 2017: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29137610/hemoglobin-stimulates-the-expression-of-adamts-5-and-adamts-9-by-synovial-cells-a-possible-cause-of-articular-cartilage-damage-after-intra-articular-hemorrhage
#4
Takuya Tajima, Tomohisa Sekimoto, Nami Yamaguchi, Noboru Taniguchi, Syuji Kurogi, Masugi Maruyama, Etsuo Chosa
BACKGROUND: ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs) proteins play an important pathological role in matrix degeneration. Aggrecan degradation is a significant and critical event in early-stage osteoarthritis. To determine the effect of hemoglobin (Hb) on the ability of synovial tissues to produce ADAMTS family members, we examined the influence of Hb by synovial cells in an in vitro experimental system. METHODS: Synovial tissues were obtained from five young patients with meniscal injury under arthroscopic surgery...
November 14, 2017: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/29137447/thrombospondin-1-is-a-multifaceted-player-in-tumor-progression
#5
REVIEW
Tingting Huang, Li Sun, Xianglin Yuan, Hong Qiu
Thrombospondins are a family of extracellular matrix (ECM) proteins. Thrombospondin-1 (TSP1) was the first member to be identified and is a main player in tumor microenvironment. The diverse functions of TSP1 depend on the interactions between its structural domains and multiple cell surface molecules. TSP1 acts as an angiogenesis inhibitor by stimulating endothelial cell apoptosis, inhibiting endothelial cell migration and proliferation, and regulating vascular endothelial growth factor bioavailability and activity...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29135310/adamts-1-4-12-and-13-levels-in-maternal-blood-cord-blood-and-placenta-in-preeclampsia
#6
Müberra Namlı Kalem, Ziya Kalem, Tuncay Yüce, Feride Soylemez
The aim of this study is to compare ADAMTS (A Disintegrin and Metalloprotease Domains with Thrombospondins motifs) 1, 4, 12, and 13 levels in maternal and cord blood and placental tissue between preeclampsia and uncomplicated pregnancies. The enzyme-linked immunosorbent assay (ELISA) results showed that ADAMTS 1, 4, 12, and 13 levels in the maternal and cord blood were lower in the preeclampsia group than in the control group. Based on the immunohistochemistry (IHC) results, ADAMTS 1, 4, and 12 levels in placental tissues were higher in the preeclampsia group...
November 14, 2017: Hypertension in Pregnancy
https://www.readbyqxmd.com/read/29130325/the-plasma-levels-of-adamts-13-von-willebrand-factor-vwfpp-and-fibrin-related-markers-in-patients-with-systemic-sclerosis-having-thrombosis
#7
Koji Habe, Hideo Wada, Ayaka Higashiyama, Tomoko Akeda, Kenshiro Tsuda, Ryoko Mori, Masato Kakeda, Takeshi Matsumoto, Kohshi Ohishi, Keiichi Yamanaka, Naoyuki Katayama, Hitoshi Mizutani
This study aimed to examine the hemostatic abnormalities in patients with systemic sclerosis (SSc) and the relationship between these abnormalities and thrombotic events (THEs), focusing on the difference in diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc). The plasma levels of ADAMTS-13 (a disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13), von Willebrand factor (VWF), VWF propeptide (VWFpp), d-dimer, and soluble fibrin (SF) were measured in 233 patients with SSc. The relationship between their levels and organ involvement, including THEs and interstitial lung disease (ILD), was evaluated...
January 1, 2017: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/29130141/sj%C3%A3-gren-s-syndrome-initially-presented-as-thrombotic-thrombocytopenic-purpura-in-a-male-patient-a-case-report-and-literature-review
#8
REVIEW
Xiaohan Xu, Tienan Zhu, Di Wu, Lu Zhang
Thrombotic thrombocytopenic purpura (TTP) is a potentially lethal multisystem disorder which could be caused by autoimmune diseases. However, the concomitant occurrence of TTP and Sjögren's syndrome (SS) is an extremely uncommon scenario, especially in male patients. A 56-year-old Chinese male was admitted for the appearance of diffuse ecchymosis. Then he gradually developed transient slurred speech, progressive confusion, agitation, extremity weakness, and fever. Laboratory investigations suggested anemia, thrombocytopenia, significantly increased lactic dehydrogenase, schistocytes in peripheral blood smear, and a disintegrin-like metalloproteinase with thrombospondin motif type 1 member 13 (ADAMTS13) activity deficiency with high inhibitor titers...
November 13, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/29123569/diagnostic-dilemma-severe-thrombotic-microangiopathy-in-pregnancy
#9
Sarah Birkhoelzer, Alexandra Belcher, Helen Peet
A diagnostic dilemma occurred when thrombotic microangiopathy developed during pregnancy. The diagnostic criteria of thrombotic microangiopathy include thrombocytopenia (platelets <100) and microangiopathic haemolytic anaemia (including thrombotic thrombocytopenic purpura and haemolytic-uraemic syndrome). An urgent interdisciplinary approach is required to treat thrombotic microangiopathy in pregnancy to differentiate between thrombotic microangiopathy and HELLP syndrome (haemolysis, elevated liver enzymes, low platelets)...
November 2017: J Intensive Care Soc
https://www.readbyqxmd.com/read/29118755/apoptotic-cells-induced-signaling-for-immune-homeostasis-in-macrophages-and-dendritic-cells
#10
REVIEW
Uriel Trahtemberg, Dror Mevorach
Inefficient and abnormal clearance of apoptotic cells (efferocytosis) contributes to systemic autoimmune disease in humans and mice, and inefficient chromosomal DNA degradation by DNAse II leads to systemic polyarthritis and a cytokine storm. By contrast, efficient clearance allows immune homeostasis, generally leads to a non-inflammatory state for both macrophages and dendritic cells (DCs), and contributes to maintenance of peripheral tolerance. As many as 3 × 10(8) cells undergo apoptosis every hour in our bodies, and one of the primary "eat me" signals expressed by apoptotic cells is phosphatidylserine (PtdSer)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29116863/hypothermia-promotes-cell-protective-and-chondroprotective-effects-after-blunt-cartilage-trauma
#11
Jana Riegger, Madeleine Zimmermann, Helga Joos, Thomas Kappe, Rolf E Brenner
BACKGROUND: Cryotherapy is routinely administered after sports injuries of synovial joints. Although positive clinical effects on periarticular swelling and pain have been described, the effects on the cell biological activities of cartilage and synovial cells remain largely unknown so far. HYPOTHESIS: Local hypothermia alleviates synovial reactions and prevents chondrocyte death as well as cartilage destructive processes after blunt cartilage trauma. STUDY DESIGN: Controlled laboratory study...
November 1, 2017: American Journal of Sports Medicine
https://www.readbyqxmd.com/read/29115522/role-of-epigenetics-in-the-pathogenesis-of-chronic-rhinosinusitis-with-nasal-polyps
#12
Jong-Yeup Kim, Dong-Kyu Kim, Myeong Sang Yu, Min-Ji Cha, Seong-Lan Yu, Jaeku Kang
Chronic rhinosinusitis (CRS) is a highly prevalent disease characterized by mucosal inflammation of the nose and paranasal sinuses. CRS can be divided into two main categories, CRS with nasal polyps (NPs; CRSwNP) and CRS without NPs (CRSsNP). Although the pathophysiology of CRS remains unclear, DNA methylation has been implicated in the etiology of CRSwNP. The aim of the present study was to elucidate whether DNA methylation of specific genes is involved in the development of NPs. In total, 18 individuals were included in the present study, and were divided into three groups: CRSwNP (n=7), CRSsNP (n=7) and healthy controls (n=4)...
November 7, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29115420/construction-of-a-prognostic-prediction-system-for-pancreatic-ductal-adenocarcinoma-to-investigate-the-key-prognostic-genes
#13
Bingli Zheng, Jie Peng, Ablikim Mollayup, Ahmat Bakri, Lei Guo, Jianjiang Zheng, Hui Xu
Pancreatic cancer (PC) is associated with high mortality rates and poor prognoses. Pancreatic adenocarcinoma is the most common type of PC, and almost all cases of pancreatic adenocarcinoma are pancreatic ductal adenocarcinoma (PDAC). The aim of the current study was to reveal the genes involved in the prognosis of PDAC. Five datasets, including GSE71729 (145 PDAC samples and 46 normal samples), GSE15471 (39 PDAC samples and 39 normal samples), GSE1542 (24 PDAC samples and 25 normal samples), GSE28735 (45 PDAC samples and 45 normal samples) and GSE62452 (69 PDAC samples and 69 normal samples) were downloaded from the Gene Expression Omnibus database...
October 20, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29109971/%C3%AE-2%C3%AE-1-signaling-drives-cell-death-synaptogenesis-circuit-reorganization-and-gabapentin-mediated-neuroprotection-in-a-model-of-insult-induced-cortical-malformation
#14
Lauren A Lau, Farzad Noubary, Dongqing Wang, Chris G Dulla
Developmental cortical malformations (DCMs) result from pre- and perinatal insults, as well as genetic mutations. Hypoxia, viral infection, and traumatic injury are the most common environmental causes of DCMs, and are associated with the subsyndromes focal polymicrogyria and focal cortical dysplasia (FCD) Type IIId, both of which have a high incidence of epilepsy. Understanding the molecular signals that lead to the formation of a hyperexcitable network in DCMs is critical to devising novel treatment strategies...
September 2017: ENeuro
https://www.readbyqxmd.com/read/29105980/extracellular-vesicles-in-the-adaptive-process-of-prostate-cancer-during-inhibition-of-androgen-receptor-signalling-by-enzalutamide
#15
Carolina Soekmadji, Anja Rockstroh, Grant A Ramm, Colleen C Nelson, Pamela J Russell
Current treatments for advanced prostate cancer focus on inhibition of the androgen receptor (AR) by androgen deprivation therapy (ADT). However, complex interactions mediated by tumour suppressors, oncogenes, aberrations of AR expression, or de novo androgen production have been shown to induce the adaptive response of prostate cancer, leading to the development of castration resistant prostate cancer (CRPC). In this study, we report the effects of AR antagonist, enzalutamide on the protein contents of extracellular vesicles (EVs)...
November 6, 2017: Proteomics
https://www.readbyqxmd.com/read/29102725/structural-modeling-of-osteoarthritis-adamts4-complex-with-its-cognate-inhibitory-protein-timp3-and-rational-derivation-of-cyclic-peptide-inhibitors-from-the-complex-interface-to-target-adamts4
#16
Wei Zhang, Biao Zhong, Chi Zhang, Yukai Wang, Shang Guo, Congfeng Luo, Yulin Zhan
The ADAMTS4 (a disintegrin and metalloproteinase with thrombospondin motifs 4) enzyme is a matrix-associated zinc metalloendopeptidase that plays an essential role in the degradation of cartilage aggrecan in arthritic diseases and has been recognized as one of the most primary targets for therapeutic intervention in osteoarthritis (OA). Here, we reported computational modeling of the atomic-level complex structure of ADAMTS4 with its cognate inhibitory protein TIMP3 based on high-resolution crystal template...
November 2, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29100277/thrombospondin-1-promotes-cell-migration-invasion-and-lung-metastasis-of-osteosarcoma-through-fak-dependent-pathway
#17
Chuanzhen Hu, Junxiang Wen, Liangzhi Gong, Xu Chen, Jun Wang, Fangqiong Hu, Qi Zhou, Jing Liang, Li Wei, Yuhui Shen, Weibin Zhang
Microenvironment at the metastatic locus usually differs greatly from that present in the site of primary tumor formation and it has a significant impact on the fate of the extravasated cancer cells. We compared gene expression signatures of primary tumors and lung metastatic tumors, and identified Thrombospondin-1 (TSP1) as highly up-regulated in the lung metastatic tumors. Immunohistochemical staining further indicated that TSP1 protein expression was higher in lung metastatic tumors compared to primary tumors in both osteosarcoma xenograft model and human clinical samples...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29098296/manipulation-of-panx1-activity-increases-the-engraftment-of-transplanted-lacrimal-gland-epithelial-progenitor-cells
#18
Liana V Basova, Xin Tang, Takeshi Umasume, Anastasia Gromova, Tatiana Zyrianova, Taisia Shmushkovich, Alexey Wolfson, Dillon Hawley, Driss Zoukhri, Valery I Shestopalov, Helen P Makarenkova
Purpose: Sjögren's syndrome is a systemic chronic autoimmune inflammatory disease that primarily targets the salivary and lacrimal glands (LGs). Currently there is no cure; therefore, cell-based regenerative therapy may be a viable option. LG inflammation is facilitated by extracellular ATP and mediated by the Pannexin-1 (Panx1) membrane channel glycoprotein. We propose that suppression of inflammation through manipulation of Panx1 activity can stimulate epithelial cell progenitor (EPCP) engraftment...
November 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29095861/identification-of-proteins-associated-with-clinical-and-pathological-features-of-proliferative-diabetic-retinopathy-in-vitreous-and-fibrovascular-membranes
#19
Ingeborg Klaassen, Ewout W de Vries, Ilse M C Vogels, Antoine H C van Kampen, Machteld I Bosscha, David H W Steel, Cornelis J F Van Noorden, Sarit Y Lesnik-Oberstein, Reinier O Schlingemann
PURPOSE: To identify the protein profiles in vitreous associated with retinal fibrosis, angiogenesis, and neurite formation in epiretinal fibrovascular membranes (FVMs) in patients with proliferative diabetic retinopathy (PDR). METHODS: Vitreous samples of 5 non-diabetic control patients with vitreous debris and 7 patients with PDR membranes were screened for 507 preselected proteins using the semi-quantitative RayBio® L-series 507 antibody array. From this array, 60 proteins were selected for a custom quantitative antibody array (Raybiotech, Human Quantibody® array), analyzing 7 control patients, 8 PDR patients with FVMs, and 5 PDR patients without FVMs...
2017: PloS One
https://www.readbyqxmd.com/read/29079545/thsd7a-associated-membranous-nephropathy-in-a-patient-with-neurofibromatosis-type-1
#20
Fujun Lin, Dan Zhang, Juan Chang, Xuanli Tang, Wenbin Guan, Gengru Jiang, Chun Zhu, Fan Bian
Target antigens in idiopathic membranous nephropathy (MN) include the phospholipase A2 receptor (PLA2R), and in some cases, the thrombospondin type 1 domain-containing 7A (THSD7A). A notable phenomenon is the high rate of cancer (reported to be as high as 20%) in patients with THSD7A-associated MN. Neurofibromatosis type 1 (NF1) is an autosomal dominant disease caused by NF1 gene mutation, and clinically characterized by multiple cutaneous neurofibromas and café-au-lait spots. In this article, we report a patient with NF1 who developed THSD7A-associated MN when the NF1 skin lesions deteriorated...
October 24, 2017: European Journal of Medical Genetics
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