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https://www.readbyqxmd.com/read/28815041/-upregulation-of-cd47-by-the-endoplasmic-reticulum-stress-pathway-controls-anti-tumor-immune-responses
#1
Katherine L Cook, David R Soto-Pantoja
We recently demonstrated that targeting the unfolded protein response (UPR) protein GRP78 down-regulates CD47 expression, resulting in increased tumor macrophage infiltration and inhibited resistance to anti-estrogen therapy. We now show new data indicating that anti-estrogen therapy regulates CD47 expression and implicates its ligand, thrombospondin-1, in regulation of tumor macrophage infiltration. Moreover, GRP78 and CD47 co-expression is associated with poor prognosis in breast cancer patients, suggesting the existence of crosstalk between UPR and immunity that regulates therapeutic responses in breast cancer...
2017: Biomarker Research
https://www.readbyqxmd.com/read/28814671/antifibrotic-role-of-vascular-endothelial-growth-factor-in-pulmonary-fibrosis
#2
Lynne A Murray, David M Habiel, Miriam Hohmann, Ana Camelo, Huilan Shang, Yang Zhou, Ana Lucia Coelho, Xueyan Peng, Mridu Gulati, Bruno Crestani, Matthew A Sleeman, Tomas Mustelin, Meagan W Moore, Changwan Ryu, Awo D Osafo-Addo, Jack A Elias, Chun G Lee, Buqu Hu, Jose D Herazo-Maya, Darryl A Knight, Cory M Hogaboam, Erica L Herzog
The chronic progressive decline in lung function observed in idiopathic pulmonary fibrosis (IPF) appears to result from persistent nonresolving injury to the epithelium, impaired restitution of the epithelial barrier in the lung, and enhanced fibroblast activation. Thus, understanding these key mechanisms and pathways modulating both is essential to greater understanding of IPF pathogenesis. We examined the association of VEGF with the IPF disease state and preclinical models in vivo and in vitro. Tissue and circulating levels of VEGF were significantly reduced in patients with IPF, particularly in those with a rapidly progressive phenotype, compared with healthy controls...
August 17, 2017: JCI Insight
https://www.readbyqxmd.com/read/28814510/a-heterologous-model-of-thrombospondin-type-1-domain-containing-7a-associated-membranous-nephropathy
#3
Nicola M Tomas, Catherine Meyer-Schwesinger, Hanning von Spiegel, Ahmed M Kotb, Gunther Zahner, Elion Hoxha, Udo Helmchen, Nicole Endlich, Friedrich Koch-Nolte, Rolf A K Stahl
Thrombospondin type 1 domain-containing 7A (THSD7A) is a target for autoimmunity in patients with membranous nephropathy (MN). Circulating autoantibodies from patients with THSD7A-associated MN have been demonstrated to cause MN in mice. However, THSD7A-associated MN is a rare disease, preventing the use of patient antibodies for larger experimental procedures. Therefore, we generated antibodies against the human and mouse orthologs of THSD7A in rabbits by coimmunization with the respective cDNAs. Injection of these anti-THSD7A antibodies into mice induced a severe nephrotic syndrome with proteinuria, weight gain, and hyperlipidemia...
August 16, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28814085/differentially-regulated-adamts1-8-and-18-in-gastric-adenocarcinoma
#4
M O Kilic, B Aynekin, A Kara, D Icen, K Demircan
OBJECTIVE: The aim is to investigate the expression status of ADAMTS1,8, and 18 proteases in gastric cancer (GC) and lymphatic metastasis. BACKGROUND: A disintegrin and metalloprotease with thrombospondin motifs (ADAMTS) is a new protease family, and has important biological functions such as hemostasis, extracellular matrix remodeling and regulation of angiogenesis. METHODS: The immunostaining status of ADAMTS1,8, and 18 were investigated in formalin-fixed paraffin-embedded samples of 25 patients who underwent curative resection for GC...
2017: Bratislavské Lekárske Listy
https://www.readbyqxmd.com/read/28810627/carthamin-yellow-inhibits-matrix-degradation-and-inflammation-induced-by-lps-in-the-intervertebral-disc-via-suppression-of-mapk-pathway-activation
#5
Bin Chen, Han-Tao Wang, Bo Yu, Ji-Dong Zhang, Yu Feng
Carthamin yellow (CY), which is a flavonoid compound isolated from safflower, has various pharmacological effects including promoting blood circulation to remove blood stasis and alleviating pain. CY is a herb used in Chinese traditional medicines. Intervertebral disc degeneration (IDD) is a common spinal disorder and degeneration of nucleus pulposus (NP) cells and inflammation are significant parts of the pathological cascade. The curative effect of CY on NP cells in association with degeneration and inflammation remains to be elucidated...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28810568/mechanism-of-microrna-146a-mediated-il-6-stat3-signaling-in-lumbar-intervertebral-disc-degeneration
#6
Tao Zhou, Hao Lin, Ziao Cheng, Chaochao Ji, Chao Zhang, Jiwei Tian
The aim of the study was to investigate the mechanism of microRNA (miR)-146a-mediated activation of interleukin-6/signal transducer and activator of transcription 3 (IL-6/STAT3) in lumbar intervertebral disc degeneration. To obtain intervertebral tissue, we recruited 5 patients with lumbar intervertebral disc herniation (experimental group) and 5 patients with lumbar burst fracture (control group). Nucleus pulposus tissue was extracted by surgery and cultured. miR-146a empty vector, mimic, and inhibitor were transfected into the two groups of cells for 24 h and the levels of IL-6, type II collagen (Col II), aggrecan, STAT3, matrix metalloproteinase (MMP)-3, and a disintegrin and metalloproteinase with thrombospondin type I motifs (ADAMTS) were detected...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28808111/interferon-tau-promotes-cell-survival-and-inhibits-specific-luteolytic-genes-in-bovine-corpus-luteum
#7
Raghavendra Basavaraja, Emilia Przygrodzka, Bartosz Pawlinski, Zdzislaw Gajewski, Monika Marzena Kaczmarek, Rina Meidan
Interferon-tau (IFNT), a maternal recognition of pregnancy signals in domestic ruminants, suppress the release of luteolytic pulses of uterine prostaglandin F2a (PGF2a), thus extending the corpus luteum (CL) life span. We hypothesized that IFNT also exerts anti-luteolytic actions in bovine CL. To examine the direct effects of IFNT on bovine CL, luteal slices and enriched luteal endothelial cells (LECs) were utilized. We found that recombinant ovine IFNT (roIFNT) markedly elevates interferon-associated genes (STAT1, STAT2, and IRF9) and interferon-stimulated genes (ISGs: MX2, ISG15, & OAS1Y) in both models...
August 14, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28807411/timp3-is-regulated-by-pericytes-upon-shear-stress-detection-leading-to-a-modified-endothelial-cell-response
#8
C Schrimpf, T Koppen, J S Duffield, U Böer, S David, W Ziegler, A Haverich, O E Teebken, M Wilhelmi
OBJECTIVES: Atherosclerosis is a hallmark of cardiovascular disease. Shear stress on endothelial cells has been linked to atherogenesis and to fibrous cap thinning and rupture. Pericytes reside in the sub-endothelial space of vessels and have vasoprotective effects. They are subjected to shear stress when endothelial cell integrity is disrupted. The aim was to investigate the susceptibility and response of pericytes to shear stress. METHODS: Endothelial cells and pericytes were seeded in two dimensional monocultures and co-cultures, and in a novel three dimensional co-culture system and were subjected to no, low and high shear stress (0, 10, 30 dyne/cm(2)) for 48 h...
August 11, 2017: European Journal of Vascular and Endovascular Surgery
https://www.readbyqxmd.com/read/28807152/structure-of-thrombospondin-type-3-repeats-in-bacterial-outer-membrane-protein-a-reveals-its-intra-repeat-disulfide-bond-dependent-calcium-binding-capability
#9
Shuyan Dai, Cancan Sun, Kemin Tan, Sheng Ye, Rongguang Zhang
Eukaryotic thrombospondin type 3 repeat (TT3R) is an efficient calcium ion (Ca(2+)) binding motif only found in mammalian thrombospondin family. TT3R has also been found in prokaryotic cellulase Cel5G, which was thought to forfeit the Ca(2+)-binding capability due to the formation of intra-repeat disulfide bonds, instead of the inter-repeat ones possessed by eukaryotic TT3Rs. In this study, we have identified an enormous number of prokaryotic TT3R-containing proteins belonging to several different protein families, including outer membrane protein A (OmpA), an important structural protein connecting the outer membrane and the periplasmic peptidoglycan layer in gram-negative bacteria...
September 2017: Cell Calcium
https://www.readbyqxmd.com/read/28804565/thrombospondin-1-inhibits-ossification-of-tissue-engineered-cartilage-constructed-by-adscs
#10
Aiguo Xie, Jixin Xue, Gan Shen, Lanjun Nie
Cartilage tissue engineering provides a new method in the treatment of cartilage defects, and adipose derived stem cells seem to be an ideal seed cell in cartilage tissue engineering because of its characteristics. However, ossification after in vivo implantation of tissue engineered cartilage remains a challenge. Thrombospondin-1 which has been reported to have an inhibitory effect on angiogenesis, may play an important role in inhibiting the ossification of tissue engineered cartilage constructed by adipose derived stem cells...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28801527/circulating-antibodies-against-thrombospondin-type-i-domain-containing-7a-in-chinese-patients-with-idiopathic-membranous-nephropathy
#11
Jia Wang, Zhao Cui, Jie Lu, Christian Probst, Yi-Miao Zhang, Xin Wang, Zhen Qu, Fang Wang, Li-Qiang Meng, Xu-Yang Cheng, Gang Liu, Hanna Debiec, Pierre Ronco, Ming-Hui Zhao
BACKGROUND AND OBJECTIVES: Thrombospondin type-I domain-containing 7A (THSD7A) was recently identified as the target antigen in about 10% of patients with M-type phospholipase A2 receptor (PLA2R)-negative membranous nephropathy in European and North American populations. The prevalence of THSD7A in other populations and their clinical associations deserve further clarification. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Immunofluorescence assay was performed to investigate anti-THSD7A antibodies in 578 consecutive patients with biopsy-proven idiopathic membranous nephropathy, 114 patients with secondary membranous nephropathy, 64 disease controls, and 20 healthy controls...
August 11, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28798097/suramin-inhibits-osteoarthritic-cartilage-degradation-by-increasing-extracellular-levels-of-chondroprotective-tissue-inhibitor-of-metalloproteinases-3-timp-3
#12
Anastasios Chanalaris, Christine Doherty, Brian D Marsden, Gabriel Bambridge, Stephen P Wren, Hideaki Nagase, Linda Troeberg
Osteoarthritis is a common degenerative joint disease for which no disease-modifying drugs are currently available. Attempts to treat the disease with small molecule inhibitors of the metalloproteinases that degrade the cartilage matrix have been hampered by a lack of specificity. We aimed to inhibit cartilage degradation by augmenting levels of the endogenous metalloproteinase inhibitor, tissue inhibitor of metalloproteinases 3 (TIMP-3), through blocking its interaction with the endocytic scavenger receptor, low-density lipoprotein receptor-related protein 1 (LRP1)...
August 10, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28795730/role-of-garp-in-the-activation-of-latent-tgf-%C3%AE-1
#13
REVIEW
Julie Stockis, Olivier Dedobbeleer, Sophie Lucas
TGF-β1, 2 and 3 cytokines are involved in many cellular processes including cell proliferation, differentiation, migration and survival. Whereas TGF-β2 and 3 play important roles in embryonic development, TGF-β1 is mostly implicated in controlling immune responses after birth. The production of TGF-β1 is a tightly regulated process, occurring mostly at a post-translational level. Virtually all cells produce the latent, inactive form of TGF-β1. In latent TGF-β1, the mature TGF-β1 dimer is non-covalently associated to the Latency Associated Peptide, or LAP, which prevents binding to the TGF-β1 receptor...
August 10, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28794454/lumican-delays-melanoma-growth-in-mice-and-drives-tumor-molecular-assembly-as-well-as-response-to-matrix-targeted-tax2-therapeutic-peptide
#14
Albin Jeanne, Valérie Untereiner, Corinne Perreau, Isabelle Proult, Cyril Gobinet, Camille Boulagnon-Rombi, Christine Terryn, Laurent Martiny, Stéphane Brézillon, Stéphane Dedieu
Lumican is a small leucine-rich proteoglycan (SLRP) being known as a key regulator of collagen fibrillogenesis. However, little attention has been given so far in studying its influence on tumor-associated matrix architecture. Here, we investigate the role of host lumican on tumor matrix organization as well as on disease progression considering an immunocompetent model of melanoma implanted in Lum (-/-) vs. wild type syngeneic mice. Conjointly, lumican impact on tumor response to matrix-targeted therapy was evaluated considering a previously validated peptide, namely TAX2, that targets matricellular thrombospondin-1...
August 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28791354/collagen-type-ii-is-downregulated-in-the-degenerative-nucleus-pulposus-and-contributes-to-the-degeneration-and-apoptosis-of-human-nucleus-pulposus-cells
#15
Chengjie Lian, Bo Gao, Zizhao Wu, Xianjian Qiu, Yan Peng, Anjing Liang, Caixia Xu, Peiqiang Su, Dongsheng Huang
Degenerative disc disease (DDD) is a common degenerative condition initiated mainly within the nucleus pulposus (NP). To date, the etiopathogenesis of DDD remains unclear, and because no effective therapeutic strategies are available to target its pathological processes, DDD is still treated with symptomatic interventions that are far from adequate. Collagen type II is one of the major matrix components of the NP, and is considered to be essential to NP homeostasis. However, the specific mechanisms by which collagen type II influences NP cells remain unknown...
August 4, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28789925/hif-1%C3%AE-represses-the-expression-of-the-angiogenesis-inhibitor-thrombospondin-2
#16
Susan C MacLauchlan, Nicole E Calabro, Yan Huang, Meenakshi Krishna, Tara Bancroft, Tanuj Sharma, Jun Yu, William C Sessa, Frank Giordano, Themis R Kyriakides
Thrombospondin-2 (TSP2) is a potent inhibitor of angiogenesis whose expression is dynamically regulated following injury. In the present study, it is shown that HIF-1α represses TSP2 transcription. Specifically, in vitro studies demonstrate that the prolyl hydroxylase inhibitor DMOG or hypoxia decrease TSP2 expression in fibroblasts. This effect is shown to be via a transcriptional mechanism as hypoxia does not alter TSP2 mRNA stability and this effect requires the TSP2 promoter. In addition, the documented repressive effect of nitric oxide (NO) on TSP2 is shown to be non-canonical and involves stabilization of HIF-1α...
August 5, 2017: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/28767721/development-and-clinical-testing-of-individual-immunoassays-for-the-quantification-of-serum-glycoproteins-to-diagnose-prostate-cancer
#17
Kathrin Endt, Jens Goepfert, Aurelius Omlin, Alcibiade Athanasiou, Pierre Tennstedt, Anna Guenther, Maurizio Rainisio, Daniel S Engeler, Thomas Steuber, Silke Gillessen, Thomas Joos, Ralph Schiess
Prostate Cancer (PCa) diagnosis is currently hampered by the high false-positive rate of PSA evaluations, which consequently may lead to overtreatment. Non-invasive methods with increased specificity and sensitivity are needed to improve diagnosis of significant PCa. We developed and technically validated four individual immunoassays for cathepsin D (CTSD), intercellular adhesion molecule 1 (ICAM1), olfactomedin 4 (OLFM4), and thrombospondin 1 (THBS1). These glycoproteins, previously identified by mass spectrometry using a Pten mouse model, were measured in clinical serum samples for testing the capability of discriminating PCa positive and negative samples...
2017: PloS One
https://www.readbyqxmd.com/read/28766346/dose-dependent-effects-of-adiponectin-on-adamts-9-gene-expression-in-human-chondrocytes
#18
K O Yaykasli, O F Hatipoglu, E Yaykasli, E Kaya, M Ozsahin, M Uslu
OBJECTIVE: A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS), comprising of 19 members is a family of peptidases. They have several vital functions in physiological and pathological processes in organisms. ADAMTS-9 has aggrecanolytic activity and is responsible for degradation of aggrecan mainly in articular cartilage. It is known that adiponectin is the most abundantly secreted adipokine (adipocytokines), and the characteristics of adiponectin have not been elucidated yet...
2017: Bratislavské Lekárske Listy
https://www.readbyqxmd.com/read/28765881/identification-of-differentially-expressed-micrornas-in-knee-anterior-cruciate-ligament-tissues-surgically-removed-from-patients-with-osteoarthritis
#19
Bin Li, Lunhao Bai, Peng Shen, Yue Sun, Zhizuo Chen, Yu Wen
The degradation of cruciate ligaments is frequently observed in degenerative joint diseases, such as osteo-arthritis (OA). The present study aimed to identify the differentially expressed microRNAs (miRNAs or miRs) in knee anterior cruciate ligament (ACL) tissues derived from patients with OA and in health subjects (non-OA). By using Affymetrix miRNA 4.0 microarrays, a total of 22 miRNAs (including let-7f-5p, miR-26b-5p and miR-146a-5p) were found to be upregulated, while 17 (including miR-18a-3p, miR-138-5p and miR-485-3p) were downregulated in the osteoarthritic ACL tissues (fold change ≥2, P-value <0...
July 31, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28765701/levels-and-activities-of-von-willebrand-factor-and-metalloproteinase-with-thrombospondin-type-1-motif-number-13-in-inflammatory-bowel-diseases
#20
Dorota Cibor, Danuta Owczarek, Saulius Butenas, Kinga Salapa, Tomasz Mach, Anetta Undas
AIM: To evaluate the levels of von Willebrand factor (VWF) and metalloproteinase with thrombospondin type-1 motif, number 13 (ADAMTS13) in inflammatory bowel disease (IBD) and correlate them with the disease activity. METHODS: Consecutive patients with IBD aged 18 years or older were enrolled in the study. Forty-seven patients with ulcerative colitis (UC), 38 with Crohn's disease (CD), and 50 healthy controls were included. The white blood cell count, haematocrit, platelet count, fibrinogen, partial activated thromboplastin time, C-reactive protein, albumin, VWF antigen level (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo), VWF collagen-binding activity (VWF:CB), and ADAMTS13 antigen level (ADAMTS13:Ag) and activity (ADAMTS13act) were measured...
July 14, 2017: World Journal of Gastroenterology: WJG
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