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https://www.readbyqxmd.com/read/29781574/melanocyte-development-in-the-mouse-tail-epidermis-requires-the-adamts9-metalloproteinase
#1
Grace Tharmarajah, Ulrich Eckhard, Fagun Jain, Giada Marino, Anna Prudova, Oscar Urtatiz, Helmut Fuchs, Martin Hrabe de Angelis, Christopher M Overall, Catherine D Van Raamsdonk
The mouse tail has an important role in the study of melanogenesis, because mouse tail skin can be used to model human skin pigmentation. To better understand the development of melanocytes in the mouse tail, we cloned two dominant ENU-generated mutations of the Adamts9 gene, Und3 and Und4, which cause an unpigmented ring of epidermis in the middle of the tail, but do not alter pigmentation in the rest of the mouse. Adamts9 encodes a widely expressed zinc metalloprotease with thrombospondin type 1 repeats with few known substrates...
May 21, 2018: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29771863/upshaw-schulman-syndrome-with-c-2728c-t-mutation-in-adamts13-gene
#2
Shahzadi Resham, Zehra Fadoo, Bushra Moiz
Congenital thrombotic thrombocytopenic purpura is a rare autosomal recessive disorder presenting with hemolytic anemia, thrombocytopenia, micro vascular thrombosis, and end organ damage. Here, we present a case of a 7-year-old girl having recurrent neonatal hemolysis, developmental delay, frequent seizures, and thrombocytopenia. Characteristic clinical picture and gene sequencing of a disintegrin and metalloproteinase with thrombospondin motifs 13 confirmed the diagnosis of Upshaw-Schulman syndrome. She was treated successfully with plasma infusion...
May 16, 2018: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29770347/precision-tagging-a-novel-seamless-protein-tagging-by-combinational-use-of-type-ii-and-type-iis-restriction-endonucleases
#3
Zhen Xu, Yan-Ning Rui, John P Hagan, Dong H Kim
Protein tagging is a powerful tool for performing comprehensive analyses of the biological functions of a protein of interest owing to the existence of a wide variety of tags. It becomes indispensable in some cases, such as in tracking protein dynamics in a live cell or adding a peptide epitope due to the lack of optimal antibodies. However, efficiently integrating an array of tags into the gene of interest remains a challenge. Traditional DNA recombinant technology based on type II restriction endonucleases renders protein tagging tedious and inefficient as well as the introduction of an unwanted junction sequence...
February 5, 2018: Bio-protocol
https://www.readbyqxmd.com/read/29769410/human-anti-thrombospondin-type-1-domain-containing-7a-antibodies-induce-membranous-nephropathy-through-activation-of-lectin-complement-pathway
#4
Zheng Wang, Lu Wen, Yanna Dou, Zhanzheng Zhao
To investigate whether the human anti-thrombospondin type 1 domain-containing 7A (THSD7A) antibody-induced membranous nephropathy is mediated by activating lectin complement pathway. Automatic biochemical apparatus was used to assess renal function of mice. The serum levels of anti-THSD7A antibodies and complement were tested by using Enzyme-linked immunosorbent assay (ELISA). The expression level of THSD7A and Mannose-Binding Lectin (MBL) in clinical tissue, and the histological features of MN in mice were examined by immunochemical methods...
May 16, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29766025/isoliquiritigenin-inhibits-il-1%C3%AE-induced-production-of-matrix-metalloproteinase-in-articular-chondrocytes
#5
Lei Zhang, Shiyun Ma, Hang Su, Jiaxiang Cheng
Osteoarthritis (OA) is a major joint disease in which inflammatory cytokine interleukin-1β (IL-1β) and matrix metalloproteinases (MMPs) play a pivotal role. Isoliquiritigenin has been reported to have anti-inflammation activity. In this study, the effect of isoliquiritigenin on IL-1β-induced production of matrix metalloproteinase and nuclear factor κB (NF-κB) activation was analyzed. We treated primary cultured articular chondrocytes with isoliquiritigenin and the expressions of MMPs were analyzed on mRNA and protein level...
June 15, 2018: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/29758118/hemostasis-biomarkers-in-multiple-sclerosis
#6
Nicole Ziliotto, Francesco Bernardi, Dejan Jakimovski, Marcello Baroni, Giovanna Marchetti, Niels Bergsland, Deepa P Ramasamy, Bianca Weinstock-Guttman, Ferdinand Schweser, Paolo Zamboni, Murali Ramanathan, Robert Zivadinov
OBJECTIVE: To investigate the plasma levels of hemostasis components in multiple sclerosis (MS) and their association with clinical and MRI outcomes. METHODS: We studied 138 MS patients (85 with relapsing-remitting, RR-MS and 53 with progressive, P-MS) with mean age of 54 years; 72.5% female; median EDSS 3.5; mean disease duration 21 years) and 42 age- and sex-matched healthy individuals (HI). All subjects were examined with 3T MRI and clinical examinations. Plasma levels of hemostasis factors (procoagulant, factor XII, FXII) and inhibitors (tissue factor pathway inhibitor (TFPI), thrombomodulin (TM), heparin cofactor II (HCII), disintegrin-like and metalloprotease with thrombospondin type 1 motif 13 (ADAMTS13), and plasminogen activator inhibitor 1 (PAI-1) were evaluated by magnetic Luminex assays and ELISA...
May 14, 2018: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/29750395/adamts-12-protects-against-inflammatory-arthritis-through-interacting-with-and-inactivating-proinflammatory-ctgf
#7
Jian-Lu Wei, Wenyu Fu, Aubryanna Hettinghouse, Wen-Jun He, Kenneth E Lipson, Chuan-Ju Liu
OBJECTIVE: It has been reported that a disintegrin and metalloproteinase with thrombospondin motifs-12 (ADAMTS-12) is a susceptibility gene for rheumatoid arthritis (RA) development, and its level is significantly increased in RA patients. In addition, ADAMTS-12 was also reported to be required for normal inflammation. This study aims to determine the role of ADAMTS-12 and the underlying mechanisms in the pathogenesis of inflammatory arthritis. METHODS: The collagen-induced arthritis (CIA) model was established in ADAMTS-12-deficient mice and their control littermates to determine the role of ADAMTS-12 in vivo; microCT scanning was used to demonstrate the destruction of ankle joint; histological analysis illustrated synovitis, pannus formation, as well as bone and cartilage destruction; ELISA was performed to measure serum levels of inflammatory cytokines; Protein-protein interaction assays were performed to detect the interactions of ADAMTS-12 and its various deletion mutants with connective tissue growth factor (CTGF)...
May 11, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29749498/detection-of-mir%C3%A2-29a-in-plasma-of-patients-with-lumbar-spinal-stenosis-and-the-clinical-significance
#8
Genai Zhang, Wenping Zhang, Yu Hou, Yingchun Chen, Jipeng Song, Lixiang Ding
The present study aimed to detect miR‑29a expression in the plasma of patients with lumbar spinal stenosis (LSS) and to investigate the clinical significance. A total of 30 patients with LSS, 27 patients with lumbar intervertebral disc herniation (LDH), 27 healthy people and 7 patients that had succumbed to mortality were involved in the present study for specimen collection. Expression levels of miR‑29a in plasma and intervertebral disc tissue were detected by reverse transcription‑quantitative polymerase chain reaction analysis...
May 3, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29748481/mdm2-overexpression-modulates-the-angiogenesis-related-gene-expression-profile-of-prostate-cancer-cells
#9
Thiagarajan Venkatesan, Ali Alaseem, Aiyavu Chinnaiyan, Sivanesan Dhandayuthapani, Thanigaivelan Kanagasabai, Khalid Alhazzani, Priya Dondapati, Saad Alobid, Umamaheswari Natarajan, Ruben Schwartz, Appu Rathinavelu
The Murine Double Minute 2 (MDM2) amplification or overexpression has been found in many tumors with high metastatic and angiogenic ability. Our experiments were designed to explore the impact of MDM2 overexpression, specifically on the levels of angiogenesis-related genes, which can also play a major role in tumor propagation and increase its metastatic potential. In the present study, we have used the human angiogenesis RT² profiler PCR array to compare the gene expression profile between LNCaP and LNCaP-MST (MDM2 transfected) prostate cancer cells, along with LNCaP-MST cells treated with Nutlin-3, an MDM2 specific inhibitor...
May 10, 2018: Cells
https://www.readbyqxmd.com/read/29737873/adamts1-and-adamts5-metalloproteases-produced-by-sertoli-cells-a-potential-diagnostic-marker-in-azoospermia
#10
Oya Sena Aydos, Yunus Yukselten, Sinan Ozkavukcu, Asuman Sunguroglu, Kaan Aydos
In this study, our aim was to detect protein levels of A Disintegrin and Metalloproteinase with Thrombospondin Motifs 1 and 5 (ADAMTS1 and ADAMTS5) proteases and to examine the effect of in vitro FSH supplementation on protease production in cultured Sertoli cells. The expression of metalloproteases, ADAMTS1, and ADAMTS5 were investigated in Sertoli cell cultures as well as in ejaculate of azoospermic men which then were compared with ejaculates of the fertile control group. A total of 15 azoospermic men, diagnosed as obstructive (OA, n = 5) and nonobstructive (NOA, n = 10) azoospermia were included in the study...
May 8, 2018: Systems Biology in Reproductive Medicine
https://www.readbyqxmd.com/read/29735912/towards-resolving-the-pro-and-anti-tumor-effects-of-the-aryl-hydrocarbon-receptor
#11
Supraja Narasimhan, Elizabeth Stanford Zulick, Olga Novikov, Ashley J Parks, Jennifer J Schlezinger, Zhongyan Wang, Fabrice Laroche, Hui Feng, Francesca Mulas, Stefano Monti, David H Sherr
We have postulated that the aryl hydrocarbon receptor (AHR) drives the later, more lethal stages of some cancers when chronically activated by endogenous ligands. However, other studies have suggested that, under some circumstances, the AHR can oppose tumor aggression. Resolving this apparent contradiction is critical to the design of AHR-targeted cancer therapeutics. Molecular (siRNA, shRNA, AHR repressor, CRISPR-Cas9) and pharmacological (AHR inhibitors) approaches were used to confirm the hypothesis that AHR inhibition reduces human cancer cell invasion (irregular colony growth in 3D Matrigel cultures and Boyden chambers), migration (scratch wound assay) and metastasis (human cancer cell xenografts in zebrafish)...
May 7, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29730901/htra1-an-age-related-macular-degeneration-protease-processes-extracellular-matrix-proteins-efemp1-and-tsp1
#12
Michael K Lin, Jin Yang, Chun Wei Hsu, Anuradha Gore, Alexander G Bassuk, Lewis M Brown, Ryan Colligan, Jesse D Sengillo, Vinit B Mahajan, Stephen H Tsang
High-temperature requirement protein A1 (HTRA1) is a serine protease secreted by a number of tissues including retinal pigment epithelium (RPE). A promoter variant of the gene encoding HTRA1 is part of a mutant allele that causes increased HTRA1 expression and contributed to age-related macular degeneration (AMD) in genomewide association studies. AMD is characterized by pathological development of drusen, extracellular deposits of proteins and lipids on the basal side of RPE. The molecular pathogenesis of AMD is not well understood, and understanding dysregulation of the extracellular matrix may be key...
May 5, 2018: Aging Cell
https://www.readbyqxmd.com/read/29729633/thrombospondin-4-mediates-cardiovascular-remodelling-in-angiotensin-ii-induced-hypertension
#13
Teresa Palao, Lejla Medzikovic, Catarina Rippe, Shaynah Wanga, Claudia Al-Mardini, Angela van Weert, Judith de Vos, Nicole N van der Wel, Henk A van Veen, Ed T van Bavel, Karl Swärd, Vivian de Waard, Erik Ntp Bakker
Thrombospondin 4 (TSP-4) expression is induced in the heart and vasculature under pathological conditions, including myocardial infarction, myocardial pressure overload, and hypertension. TSP-4 is linked to remodelling processes, where it may affect extracellular matrix protein organization. In previous work, we studied the role of TSP-4 in small arteries during hypertension using Ang II-treated Thrombospondin 4 knockout (Thbs4-/- ) mice. We reported increased heart weight, as well as the occurrence of aortic aneurysms in the Ang II-treated Thbs4-/- animals...
April 7, 2018: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
https://www.readbyqxmd.com/read/29712757/defective-flux-of-thrombospondin-4-through-the-secretory-pathway-impairs-cardiomyocyte-membrane-stability-and-causes-cardiomyopathy
#14
Matthew J Brody, Davy Vanhoutte, Tobias G Schips, Justin G Boyer, Chinmay V Bakshi, Michelle A Sargent, Allen J York, Jeffery D Molkentin
Thrombospondins are stress-inducible secreted glycoproteins with critical functions in tissue injury and healing. Thrombospondin-4 (Thbs4) is protective in cardiac and skeletal muscle where it activates an adaptive endoplasmic reticulum (ER) stress-response, induces expansion of the ER, and enhances sarcolemmal stability. However, it is unclear if Thbs4 has these protective functions from within the cell, from the extracellular matrix, or from the secretion process itself. Here we generated transgenic mice with cardiac-specific overexpression of a secretion-defective mutant of Thbs4 to evaluate its exclusive intracellular and secretion-dependent functions...
April 30, 2018: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/29702061/aggrecanase-degradation-of-type-iii-collagen-is-associated-with-clinical-knee-pain
#15
A C Bay-Jensen, C F Kjelgaard-Petersen, K K Petersen, L Arendt-Nielsen, H L Quasnichka, A Mobasheri, M A Karsdal, D J Leeming
There is a lack of biochemical markers for non-invasive and objective assessment of symptomatic osteoarthritis (OA). Aggrecanase activity has been shown to be associated with joint deterioration and symptomatic disease through the degradation of extracellular matrix proteins, such as type III collagen. Our study aimed to identify and develop a novel biomarker by measuring an aggrecanase-mediated type III collagen neoepitope, and correlate levels of this biomarker with OA joint pain. Mass spectrometric analysis of purified type III collagen, degraded by the aggrecanase A Disintigrin and Metalloproteinase with Thrombospondin motif (ADAMTS), revealed a fragment generated by ADAMTS-1, -4 and -8...
April 24, 2018: Clinical Biochemistry
https://www.readbyqxmd.com/read/29701048/-mechanism-of-thermosensitive-moxibustion-on-knee-osteoarthritis-in-rabbit-models
#16
Yong Fu, Shutao Chen, Jiaona Mao, Yi Pan, Chao Huang, Jun Xiong, Chunchuan Yan, Xiaodong Huang, Haifeng Zhang
OBJECTIVE: To observe the impacts of thermosensitive moxibustion (TSM) on the expressions of nitric oxide (NO), typeⅠdisintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4), typeⅡcollagen and proteoglycan (PG) in the rabbit models of knee osteoarthritis (KOA) and explore the mechanism of TSM on KOA. METHODS: A total of 42 Japanese long-eared male rabbits were divided into a blank group (6 rabbits), a model group (6 rabbits), a moxibustion group (24 rabbits) and a sham-operation group (6 rabbits) according to the random number table...
March 12, 2018: Zhongguo Zhen Jiu, Chinese Acupuncture & Moxibustion
https://www.readbyqxmd.com/read/29695980/cardiac-remodeling-endothelial-cells-have-more-to-say-than-just-no
#17
REVIEW
Vincent F M Segers, Dirk L Brutsaert, Gilles W De Keulenaer
The heart is a highly structured organ consisting of different cell types, including myocytes, endothelial cells, fibroblasts, stem cells, and inflammatory cells. This pluricellularity provides the opportunity of intercellular communication within the organ, with subsequent optimization of its function. Intercellular cross-talk is indispensable during cardiac development, but also plays a substantial modulatory role in the normal and failing heart of adults. More specifically, factors secreted by cardiac microvascular endothelial cells modulate cardiac performance and either positively or negatively affect cardiac remodeling...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29694979/promotion-of-tumor-growth-by-adamts4-in-colorectal-cancer-focused-on-macrophages
#18
Jianjun Chen, Yang Luo, Yong Zhou, Shaolan Qin, Yier Qiu, Ran Cui, Minhao Yu, Jun Qin, Ming Zhong
BACKGROUND/AIMS: ADAMTSs (A disintegrin and metalloprotease domains with thrombospondins motifs) are a family of extracellular proteases that have been related to both oncogenic and tumor-suppressive functions. The aim of the present study was to investigate: 1) the mutation, copy-number alterations, and expression profile of ADAMTSs in colorectal cancer and 2) whether ADAMTSs participate in colorectal cancer (CRC) progression and invasion. METHODS: The mutation, copy-number alterations, and expression profile of ADAMTSs in CRC were analyzed in the TCGA cohort using cBioportal...
April 20, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29691281/loss-of-fgfr1-in-chondrocytes-inhibits-osteoarthritis-through-promoting-autophagic-activity-in-temporomandibular-joint
#19
Zuqiang Wang, Junlan Huang, Siru Zhou, Fengtao Luo, Qiaoyan Tan, Xianding Sun, Zhenhong Ni, Hangang Chen, Xiaolan Du, Yangli Xie, Lin Chen
Temporomandibular joint osteoarthritis (TMJ OA) is common degenerative disease with few effective disease-modifying treatments in clinic. Fibroblast growth factor (FGF) signaling is implicated in articular cartilage homeostasis, but the functional roles of FGFR1 in TMJ OA remain largely unknown. In this study, we report that deletion of Fgfr1 in TMJ chondrocytes delayed the TMJ OA progression in age-associated spontaneous OA model and abnormal dental occlusion OA model. Immunohistochemical staining revealed that Fgfr1 deficiency decreased the expressions of matrix metalloproteinase-13 (MMP13),A disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) , COL10A1, while increased aggrecan expression level in two TMJ OA models...
April 24, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29684582/platelet-microparticle-delivered-microrna-let-7a-promotes-the-angiogenic-switch
#20
Chinedu Anene, Anne M Graham, James Boyne, Wayne Roberts
Platelet microparticle (PMP)-induced angiogenesis plays a key role in tumour metastasis and has been proposed to contribute towards cardiovascular disease by enhancing atherosclerotic plaque vulnerability. However, the mechanisms underlying PMP induced angiogenesis are ill defined. Recent reports demonstrate that PMPs deliver micro-RNAs (miRNAs) to recipient cells, controlling gene expression. We therefore evaluated whether miRNA transfer was a key regulator of PMP-induced angiogenesis. Co-culturing PMPs with human umbilical vein endothelial cells (HUVEC) on extracellular matrix gel induced robust capillary like structure formation...
April 20, 2018: Biochimica et Biophysica Acta
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