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Shao-Yong Xu, Shu-Fen Li, Guo-Xin Ni
BACKGROUND Although tendinopathy is common, its underlying pathogenesis is poorly understood. This study aimed to investigate the possible pathogenesis of tendinopathy. MATERIAL AND METHODS In this study, a total of 24 rats were randomly and evenly divided into a control (CON) group and a strenuous treadmill running (STR) group. Animals in the STR group were subjected to a 12-week treadmill running protocol. Subsequently, all Achilles tendons were harvested to perform histological observation or biochemical analyses...
October 15, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Jannie M B Sand, Diana J Leeming, Inger Byrjalsen, Asger R Bihlet, Peter Lange, Ruth Tal-Singer, Bruce E Miller, Morten A Karsdal, Jørgen Vestbo
BACKGROUND: There is a need to identify individuals with COPD at risk for disease progression and mortality. Lung tissue remodeling is associated with the release of extracellular matrix (ECM) fragments into the peripheral circulation. We hypothesized that ECM remodeling was associated with mortality in COPD and measured neo-epitopes originating from ECM proteins associated with lung tissue remodeling. METHODS: Biomarkers of ECM remodeling were assessed in a subpopulation (n = 1000) of the Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) cohort...
October 4, 2016: Respiratory Research
Tomislav Sarenac, Martin Trapecar, Lidija Gradisnik, Marjan Slak Rupnik, Dusica Pahor
Corneal wound healing is often affected by TGF-β-mediated fibrosis and scar formation. Guided fibrosis with IGF-1 and antifibrotic substances might maintain corneal transparency. Primary human corneal keratocytes under serum-free conditions were used as a model of corneal stromal wounding, with markers of corneal fibrosis and opacity studied under TGF-β2 stimulation. Single-cell imaging flow cytometry was used to determine nuclearization of Smad3, and intracellular fluorescence intensity of Smad7 and the corneal crystallin aldehyde dehydrogenase 3A1...
September 30, 2016: Scientific Reports
Josephina A N Meester, Geert Vandeweyer, Isabel Pintelon, Martin Lammens, Lana Van Hoorick, Simon De Belder, Kathryn Waitzman, Luciana Young, Larry W Markham, Julie Vogt, Julie Richer, Luc M Beauchesne, Sheila Unger, Andrea Superti-Furga, Milan Prsa, Rami Dhillon, Edwin Reyniers, Harry C Dietz, Wim Wuyts, Geert Mortier, Aline Verstraeten, Lut Van Laer, Bart L Loeys
PURPOSE: Thoracic aortic aneurysm and dissection (TAAD) is typically inherited in an autosomal dominant manner, but rare X-linked families have been described. So far, the only known X-linked gene is FLNA, which is associated with the periventricular nodular heterotopia type of Ehlers-Danlos syndrome. However, mutations in this gene explain only a small number of X-linked TAAD families. METHODS: We performed targeted resequencing of 368 candidate genes in a cohort of 11 molecularly unexplained Marfan probands...
September 15, 2016: Genetics in Medicine: Official Journal of the American College of Medical Genetics
Emily Fuller, Christopher B Little, James Melrose
We have developed an ovine meniscal explant model where the focal degradative events leading to characteristic fragmentation patterns of biglycan in human OA of the knee and hip, and evident in animal models of knee OA and IVD degeneration are reproduced in culture. Lateral and medial menisci were dissected into outer, mid and inner zones and established in explant culture±IL-1 (10ng/ml). The biglycan species present in conditioned media samples and in GuHCl extracts of tissues were examined by Western blotting using two C-terminal antibodies PR-85 and EF-Bgn...
September 9, 2016: Experimental and Molecular Pathology
Helena Frey, Kristin Moreth, Louise Tzung-Harn Hsieh, Jinyang Zeng-Brouwers, Birgit Rathkolb, Helmut Fuchs, Valérie Gailus-Durner, Renato V Iozzo, Martin Hrabě de Angelis, Liliana Schaefer
Secondary polycythemia, a disease characterized by a selective increase in circulating mature erythrocytes, is caused by enhanced erythropoietin (Epo) concentrations triggered by hypoxia-inducible factor-2α (HIF-2α). While mechanisms of hypoxia-dependent stabilization of HIF-2α protein are well established, data regarding oxygen-independent regulation of HIF-2α are sparse. In this study, we generated a novel transgenic mouse model, in which biglycan was constitutively overexpressed and secreted by hepatocytes (BGN (Tg)), thereby providing a constant source of biglycan released into the blood stream...
September 6, 2016: Glycoconjugate Journal
Lei Hu, Ming-de Zang, He-Xiao Wang, Jian-Fang Li, Li-Ping Su, Min Yan, Chen Li, Qiu-Meng Yang, Bing-Ya Liu, Zheng-Gang Zhu
Biglycan (BGN) is an important component of the extracellular matrix (ECM) that is implicated in a variety of human cancers. In our previous study, we reported that BGN was overexpressed in gastric cancer (GC) tissues and promoted cancer metastasis. Moreover, the tubular formation capacity in HUVECs was promoted by stimulation with culture media from BGN-overexpressing GC cells, but the exact underlying mechanism is still unknown. The purpose of this study was to determine the role and molecular mechanism of BGN in VEGF expression in endothelial cells...
November 2016: Molecular Oncology
Takato Hara, Eiko Yoshida, Yasuhiro Shinkai, Chika Yamamoto, Yasuyuki Fujiwara, Yoshito Kumagai, Toshiyuki Kaji
Proteoglycans are macromolecules that consist of a core protein and one or more glycosaminoglycan side chains. A small leucine-rich dermatan sulfate proteoglycan, biglycan, is one of the predominant types of proteoglycans synthesized by vascular endothelial cells; however, the physiological functions of biglycan are not completely understood. In the present study, bovine aortic endothelial cells in culture were transfected with small interfering RNAs for biglycan, and the expression of other proteoglycans was examined...
September 1, 2016: Journal of Cellular Biochemistry
Jihane Frikeche, George Maiti, Shukti Chakravarti
The small leucine rich repeat proteoglycans are major components of the cornea. Lumican, keratocan, decorin, biglycan and osteoglycin are present throughout the adult corneal stroma, and fibromodulin in the peripheral limbal area. In the cornea literature these proteoglycan have been reviewed as structural, collagen fibril-regulating proteins of the cornea. However, these proteoglycans are members of the leucine-rich-repeat superfamily, and share structural similarities with pathogen recognition toll-like receptors...
October 2016: Experimental Eye Research
Javier Barallobre-Barreiro, Shashi K Gupta, Anna Zoccarato, Rika Kitazume-Taneike, Marika Fava, Xiaoke Yin, Tessa Werner, Marc N Hirt, Anna Zampetaki, Alessandro Viviano, Mei Chong, Marshall Bern, Antonios Kourliouros, Nieves Domenech, Peter Willeit, Ajay M Shah, Marjan Jahangiri, Liliana Schaefer, Jens W Fischer, Renato V Iozzo, Rosa Viner, Thomas Thum, Joerg Heineke, Antoine Kichler, Kinya Otsu, Manuel Mayr
BACKGROUND: Myocardial fibrosis is a feature of many cardiac diseases. We used proteomics to profile glycoproteins in the human cardiac extracellular matrix (ECM). METHODS: Atrial specimens were analyzed by mass spectrometry after extraction of ECM proteins and enrichment for glycoproteins or glycopeptides. RESULTS: ECM-related glycoproteins were identified in left and right atrial appendages from the same patients. Several known glycosylation sites were confirmed...
September 13, 2016: Circulation
Hiroko Habuchi, Takahiro Ushida, Osami Habuchi
BACKGROUND: Chondroitin/dermatan sulfate (CS/DS) rich in N-acetylgalactosamine 4,6-bissulfate (GalNAc(4,6SO4)) residues is present as decorin and/or biglycan in mouse liver, and GalNAc(4,6SO4) residues disappeared completely in N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase (GalNAc4S-6ST) knockout (KO) mice. The aim of this study was to investigate whether CS/DS rich in GalNAc(4,6SO4) residues participate in the progression or resolution of liver fibrosis. METHODS: Wild type (WT) and GalNAc4S-6ST KO mice were treated with CCl4 for 5 weeks...
August 2016: Heliyon
Ivan Mikšík, Pavla Sedláková, Statis Pataridis, Federica Bortolotti, Rossella Gottardo
Proteins and their modifications of the natural mummy of Cangrande della Scala (Prince of Verona, Northern Italy, 1291-1329) were studied. The nano-LC-Q-TOF analysis of samples of rib bone and muscle from the mummy showed the presence of different proteins including type I, III IV, V and XI collagen, haemoglobin (subunits alpha and beta), ferritin, biglycan, vitronectin, prothrombin and osteocalcin. The structure of type I and type III collagen was deeply studied in order to evaluate the occurrence of modifications in comparison with type I and type III collagen coming from tissues of recently died people...
August 20, 2016: Protein Science: a Publication of the Protein Society
Pingbo Zhang, Rabia Karani, Randi L Turner, Craig Dufresne, Sara Ferri, Jennifer E Van Eyk, Richard D Semba
The optic nerve is a white matter tract that conveys visual information to the brain. The sclera comprises the white, protective outer layer of the eye. A characterization of the proteome of normal human retrobulbar optic nerve and sclera may facilitate studies of the eye. We conducted a proteomic analysis of optic nerve and sclera from five adults. Proteins were fractionated using SDS-PAGE. After in-gel digestion, peptides were analyzed using LC-MS/MS on an Orbitrap Elite mass spectrometer. We identified 2711 non-redundant proteins in retrobulbar optic nerve and 1945 non-redundant proteins in sclera...
October 2016: Proteomics
Renáta Gáspár, Márton Pipicz, Fatime Hawchar, Dávid Kovács, Luna Djirackor, Anikó Görbe, Zoltán V Varga, Mónika Kiricsi, Goran Petrovski, Attila Gácser, Csaba Csonka, Tamás Csont
AIMS: Exogenously administered biglycan (core protein with high-molecular weight glycosaminoglycan chains) has been shown to protect neonatal cardiomyocytes against simulated ischemia/reperfusion injury (SI/R), however, the mechanism of action is not clear. In this study we aimed to investigate, which structural component of biglycan is responsible for its cardiocytoprotective effect and to further explore the molecular mechanisms involved in the cytoprotection. METHODS AND RESULTS: A pilot study was conducted to demonstrate that both native (glycanated) and deglycanated biglycan can attenuate cell death induced by SI/R in a dose-dependent manner in primary neonatal cardiomyocytes isolated from Wistar rats...
August 9, 2016: Journal of Molecular and Cellular Cardiology
Loren E Dupuis, Lorna Doucette, A Kittrell Rice, Ashton E Lancaster, Matthew G Berger, Shukti Chakravarti, Christine B Kern
BACKGROUND: There are many patients that exhibit connective tissue related cardiac malformations but do not have mutations in collagen genes. The Small Leucine Rich Proteoglycans (SLRP) fibromodulin (FMOD) and lumican (LUM) bind collagen and regulate fibril assembly in other biological contexts. RESULTS: FMOD deficient mice and double deficient FMOD; LUM mice exhibited anomalies in regions where cardiac valve tissue interdigitates with adjacent muscle for support...
October 2016: Developmental Dynamics: An Official Publication of the American Association of Anatomists
Mikako Ito, Yuka Ehara, Shin Li, Kosuke Inada, Kinji Ohno
Duchenne muscular dystrophy (DMD) is a devastating muscle disease caused by loss-of-function mutations in <i>DMD</i> encoding dystrophin. No rational therapy is currently available. Utrophin is a paralog of dystrophin and is highly expressed at the neuromuscular junction. In <i>mdx</i> mice, utrophin is naturally upregulated throughout the muscle fibers, which mitigates muscular dystrophy. We previously reported the protein-anchoring therapy, in which a recombinant extracellular matrix protein is delivered to and anchored to a specific target using its proprietary binding domains...
August 2, 2016: Human Gene Therapy
Jimin Kim, Seul Ki Lee, Ji-Min Shin, Un-Woo Jeoun, Yeon Jin Jang, Hye Soon Park, Jong-Hyeok Kim, Gyung-Yub Gong, Taik Jong Lee, Joon Pio Hong, Yeon Ji Lee, Yoon-Suk Heo
Extracellular matrix (ECM) remodeling dynamically occurs to accommodate adipose tissue expansion during obesity. One non-fibrillar component of ECM, biglycan, is released from the matrix in response to tissue stress; the soluble form of biglycan binds to toll-like receptor 2/4 on macrophages, causing proinflammatory cytokine secretion. To investigate the pattern and regulatory properties of biglycan expression in human adipose tissues in the context of obesity and its related diseases, we recruited 21 non-diabetic obese women, 11 type 2 diabetic obese women, and 59 normal-weight women...
2016: Scientific Reports
Katharina Röck, Simon Andreas Joosse, Julia Müller, Nina Heinisch, Nicola Fuchs, Michael Meusch, Petra Zipper, Julia Reifenberger, Klaus Pantel, Jens Walter Fischer
Chronic UVB-exposure and declined estradiol production after menopause represent important factors leading to extrinsic and intrinsic aging, respectively. Remodeling of the extracellular matrix (ECM) plays a crucial role in both responses. Whether the dermal ECM is able to recover after cessation of UVB-irradiation in dependence of estradiol is not known, however of relevance when regarding possible treatment options. Therefore, the endogenous sex hormone production was depleted by ovariectomy in female mice...
2016: Scientific Reports
Alison M Muir, Dawiyat Massoudi, Ngon Nguyen, Douglas R Keene, Se-Jin Lee, David E Birk, Jeffrey M Davidson, M Peter Marinkovich, Daniel S Greenspan
Closely related extracellular metalloproteinases bone morphogenetic protein 1 (BMP1) and mammalian Tolloid-like 1 (mTLL1) are co-expressed in various tissues and have been suggested to have overlapping roles in the biosynthetic processing of extracellular matrix components. Early lethality of mice null for the BMP1 gene Bmp1 or the mTLL1 gene Tll1 has impaired in vivo studies of these proteinases. To overcome issues of early lethality and functional redundancy we developed the novel BT(KO) mouse strain, with floxed Bmp1 and Tll1 alleles, for induction of postnatal, simultaneous ablation of the two genes...
June 27, 2016: Matrix Biology: Journal of the International Society for Matrix Biology
Nako Maishi, Yusuke Ohba, Kosuke Akiyama, Noritaka Ohga, Jun-Ichi Hamada, Hiroko Nagao-Kitamoto, Mohammad Towfik Alam, Kazuyuki Yamamoto, Taisuke Kawamoto, Nobuo Inoue, Akinobu Taketomi, Masanobu Shindoh, Yasuhiro Hida, Kyoko Hida
Tumour blood vessels are gateways for distant metastasis. Recent studies have revealed that tumour endothelial cells (TECs) demonstrate distinct phenotypes from their normal counterparts. We have demonstrated that features of TECs are different depending on tumour malignancy, suggesting that TECs communicate with surrounding tumour cells. However, the contribution of TECs to metastasis has not been elucidated. Here, we show that TECs actively promote tumour metastasis through a bidirectional interaction between tumour cells and TECs...
2016: Scientific Reports
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