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Yoshiaki Okuma, Kenji Suda, Hideyuki Nakaoka, Yasuhiro Katsube, Yoshihide Mitani, Yukako Yoshikane, Fukiko Ichida, Takeji Matsushita, Hiroyuki Shichino, Isao Shiraishi, Jun Abe, Michiaki Hiroe, Toshimichi Yoshida, Kyoko Imanaka-Yoshida
BACKGROUND: Tenascin-C (TN-C) is an extracellular matrix glycoprotein that is heavily upregulated at sites of inflammation. We conducted a retrospective study to assess the utility of TN-C as a novel biomarker to predict the risk of developing coronary artery lesions (CAL) and resistance to intravenous immunoglobulin (IVIG) in patients with Kawasaki disease (KD).Methods and Results:We collected blood samples of 111 KD patients (IVIG-responder: 89, IVIG-resistant: 22; CAL: 8) and 23 healthy controls, and measured the serum levels of TN-C...
October 15, 2016: Circulation Journal: Official Journal of the Japanese Circulation Society
Sayaka Myojin, Takeru Yoshimura, Shigeo Yoshida, Atsunobu Takeda, Yusuke Murakami, Yoichi Kawano, Yuji Oshima, Tatsuro Ishibashi, Koh-Hei Sonoda
PURPOSE: The analysis of gene expression in idiopathic epiretinal membranes (iERMs) may help elucidate ERM formation and its pathology. Here, we conducted a case-control study, in order to determine the expression levels of cytokines and other genes in eyes with macular hole (MH) or iERM. METHODS: Twenty eyes, obtained from seven male and 13 female patients, were included in the study. The average age of the study subjects was 69.1 ± 7.67 years, and 15 eyes had iERM, while five eyes had MH...
2016: PloS One
Karen Stanic, Natalia Saldivia, Benjamín Förstera, Marcela Torrejón, Hernán Montecinos, Teresa Caprile
Extracellular matrix (ECM) molecules are pivotal for central nervous system (CNS) development, facilitating cell migration, axonal growth, myelination, dendritic spine formation, and synaptic plasticity, among other processes. During axon guidance, the ECM not only acts as a permissive or non-permissive substrate for navigating axons, but also modulates the effects of classical guidance cues, such as netrin or Eph/ephrin family members. Despite being highly important, little is known about the expression of ECM molecules during CNS development...
2016: Frontiers in Neuroanatomy
Katrin Gutsche, Elisa Randi, Volker Blank, Daniel Fink, Roland H Wenger, Cornelia Leo, Carsten C Scholz
Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer. Treatment options are limited and the mechanisms underlying its aggressiveness are poorly understood. Intermittent hypoxia (IH) causes oxidative stress and is emerging as important regulator of tumor metastasis. Vessels in IBC tumors have been shown to be immature, which is a primary cause of IH. We therefore investigated the relevance of IH for the modulation of gene expression in IBC cells in order to assess IH as potential regulator of IBC aggressiveness...
October 5, 2016: Free Radical Biology & Medicine
Noriko Horii-Hayashi, Takayo Sasagawa, Mayumi Nishi
The hypothalamus controls metabolism, stress responses, and instinctive behaviors for individual survival and species preservation. Recent studies suggest that hypothalamic neurons retain plasticity throughout adulthood, which enables these neurons to respond to various kinds of changes in environment, nutrients, and fluctuating hormones. One of the mechanisms underlying the regulation of neural plasticity is the formation of a stable extracellular matrix (ECM) structure called perineuronal nets (PNNs). PNNs are large aggregates of heterogeneous ECM molecules such as chondroitin sulfate proteoglycans (CSPGs), hyaluronan, their link proteins, and tenascin-R...
October 6, 2016: Anatomical Science International
Martin Hagedorn, Géraldine Siegfried, Katarzyna B Hooks, Abdel-Majid Khatib
Tissue regeneration requires expression of a large, unknown number of genes to initiate and maintain cellular processes such as proliferation, extracellular matrix synthesis, differentiation and migration. A unique model to simulate this process in a controlled manner is the re-growth of the caudal fin of zebrafish after amputation. Within this tissue stem cells differentiate into fibroblasts, epithelial and endothelial cells as well as melanocytes. Many genes implicated in the regeneration process are deregulated in cancer...
September 26, 2016: Oncotarget
Yoshiyuki Kobayashi, Shigeo Yoshida, Yedi Zhou, Takahito Nakama, Keijiro Ishikawa, Yuki Kubo, Mitsuru Arima, Shintaro Nakao, Toshio Hisatomi, Yasuhiro Ikeda, Akira Matsuda, Koh-Hei Sonoda, Tatsuro Ishibashi
Tenascin-C is expressed in choroidal neovascular (CNV) membranes in eyes with age-related macular degeneration (AMD). However, its role in the pathogenesis of CNV remains to be elucidated. Here we investigated the role of tenascin-C in CNV formation. In immunofluorescence analyses, tenascin-C co-stained with α-SMA, pan-cytokeratin, CD31, CD34, and integrin αV in the CNV membranes of patients with AMD and a mouse model of laser-induced CNV. A marked increase in the expression of tenascin-C mRNA and protein was observed 3 days after laser photocoagulation in the mouse CNV model...
September 26, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
Zhe Wu Jin, Shunichi Shibata, Hiroshi Abe, Yu Jin, Xiang Wu Li, Gen Murakami
Using longitudinal semiserial sections of 12 lower extremities from 8 human fetuses at 15-18 weeks, we compared fetal morphologies of the knee in specimens with and without fabellae. We also compared the fabella, if present, with the hallucal sesamoid in the same fetus. Cartilaginous fabella, positive for versican and tenascin by immunohistochemistry, was found in 5 of the 8 fetuses. This structure was embedded in a thick and tight lateral fibrous band, providing a common origin of the plantaris muscle and the lateral head of the gastrocnemius muscle...
September 26, 2016: Folia Morphologica (Warsz)
Thomas Fröhlich, Elisabeth Kemter, Florian Flenkenthaler, Nikolai Klymiuk, Kathrin A Otte, Andreas Blutke, Sabine Krause, Maggie C Walter, Rüdiger Wanke, Eckhard Wolf, Georg J Arnold
Duchenne muscular dystrophy (DMD) is caused by genetic deficiency of dystrophin and characterized by massive structural and functional changes of skeletal muscle tissue, leading to terminal muscle failure. We recently generated a novel genetically engineered pig model reflecting pathological hallmarks of human DMD better than the widely used mdx mouse. To get insight into the hierarchy of molecular derangements during DMD progression, we performed a proteome analysis of biceps femoris muscle samples from 2-day-old and 3-month-old DMD and wild-type (WT) pigs...
2016: Scientific Reports
Janina Burk, Amelie Plenge, Walter Brehm, Sandra Heller, Bastian Pfeiffer, Cornelia Kasper
Tendon and ligament pathologies are still a therapeutic challenge, due to the difficulty in restoring the complex extracellular matrix architecture and biomechanical strength. While progress is being made in cell-based therapies and tissue engineering approaches, comprehensive understanding of the fate of progenitor cells in tendon healing is still lacking. The aim of this study was to investigate the effect of decellularized tendon matrix and moderate cyclic stretching as natural stimuli which could potentially direct tenogenic fate...
2016: Stem Cells International
Haiyan Fu, Yuan Tian, Lili Zhou, Dong Zhou, Roderick J Tan, Donna B Stolz, Youhua Liu
Kidney fibrosis initiates at certain focal sites in which the fibrogenic niche provides a specialized microenvironment that facilitates fibroblast activation and proliferation. However, the molecular identity of these fibrogenic niches is poorly characterized. Here, we determined whether tenascin-C (TNC), an extracellular matrix glycoprotein, is a component of the fibrogenic niche in kidney fibrosis. In vivo, TNC expression increased rapidly in kidneys subjected to unilateral ureteral obstruction or ischemia/reperfusion injury and predominantly localized at the foci rich in fibroblasts in renal interstitium...
September 9, 2016: Journal of the American Society of Nephrology: JASN
Victoria Catalán, Javier Gómez-Ambrosi, Amaia Rodríguez, Beatriz Ramírez, Maitane Izaguirre, José Luis Hernández-Lizoain, Jorge Baixauli, Pablo Martí, Víctor Valentí, Rafael Moncada, Camilo Silva, Javier Salvador, Gema Frühbeck
BACKGROUND: Excess adipose tissue represents a major risk factor for the development of colon cancer with inflammation and extracellular matrix (ECM) remodeling being proposed as plausible mechanisms. The aim of this study was to investigate whether obesity can influence circulating levels of inflammation-related extracellular matrix proteins in patients with colon cancer (CC), promoting a microenvironment favorable for tumor growth. METHODS: Serum samples obtained from 79 subjects [26 lean (LN) and 53 obese (OB)] were used in the study...
2016: PloS One
Lan-Xin Zhang, Kun-Feng Li, Huan Wang, Meng-Jie Gu, Li-Si Liu, Zhuo-Zhao Zheng, Nan-Yin Han, Zhen-Jun Yang, Tian-Yuan Fan
The aim of this study was to prepare aptamer-modified liposomes loaded with gadolinium (Gd) to enhance the effective diagnosis for tumor by MRI. A modified GBI-10 (GBI-10m) was used to prepare targeted liposomes (GmLs). Liposomes with GBI-10 aptamer (GLs) and without aptamer (non-targeted liposomes (NLs)) were also prepared as controls. The particle size and zeta potential of GmLs, GLs, and NLs were all assayed. A clinical 3.0 T MR scanner was employed to assess the imaging efficiency and measure the longitudinal relaxivity (r 1) of the above liposomes...
September 7, 2016: AAPS PharmSciTech
Ravi Thakur, Durga Prasad Mishra
Matricellular proteins (MCPs) are the non-structural extracellular matrix (ECM) proteins with various regulatory functions. MCPs are critical regulators of ECM homeostasis and are often found dysregulated in various malignancies. They interact with various ECM structural proteins like integrins, growth factor receptors and growth factors to modulate their availability and activity. Cancer supporting MCPs are known to induce proliferation, migration and invasion of cancer cells. MCPs also support cancer stem (like) cell growth and induce a drug resistant state...
September 2, 2016: Pharmacology & Therapeutics
Jos L J van der Velden, Ying Ye, James D Nolin, Sidra M Hoffman, David G Chapman, Karolyn G Lahue, Sarah Abdalla, Peng Chen, Yong Liu, Brydon Bennett, Nasreen Khalil, Donna Sutherland, William Smith, Gerald Horan, Mahmoud Assaf, Zebulun Horowitz, Rajesh Chopra, Randall M Stevens, Maria Palmisano, Yvonne M W Janssen-Heininger, Peter H Schafer
BACKGROUND: Lung remodeling and pulmonary fibrosis are serious, life-threatening conditions resulting from diseases such as chronic severe asthma and idiopathic pulmonary fibrosis (IPF). Preclinical evidence suggests that JNK enzyme function is required for key steps in the pulmonary fibrotic process. However, a selective JNK inhibitor has not been investigated in translational models of lung fibrosis with clinically relevant biomarkers, or in IPF patients. METHODS: The JNK inhibitor CC-930 was evaluated in the house dust mite-induced fibrotic airway mouse model, in a phase I healthy volunteer pharmacodynamic study, and subsequently in a phase II multicenter study of mild/moderate IPF (n = 28), with a 4-week, placebo-controlled, double-blind, sequential ascending-dose period (50 mg QD, 100 mg QD, 100 mg BID) and a 52-week open-label treatment-extension period...
December 2016: Clinical and Translational Medicine
Serwet Demirdas, Eelco Dulfer, Leema Robert, Marlies Kempers, Daphne van Beek, Dimitra Micha, Baziel G van Engelen, Ben Hamel, Joost Schalkwijk, Bart Loeys, Alessandra Maugeri, Nicol C Voermans
The tenascin-X (TNX) deficient type Ehlers-Danlos syndrome (EDS) is similar to the classical type of Ehlers-Danlos syndrome. Due to the limited awareness among geneticists and the challenge of the molecular analysis of the TNXB gene, the TNX-deficient type EDS is likely to be under diagnosed. We therefore performed an observational, cross-sectional study. History and physical examination were performed. Results of serum TNX measurements were collected and mutation analysis was performed by a combination of NGS, Sanger sequencing and MLPA...
September 1, 2016: Clinical Genetics
Yu Chen, Zi-Feng Chen, Fan He
OBJECTIVE: To understand the mechanism by which tenascin-C regulates osteoblast differentiation and the role of tenascin-C in osteoporosis. METHODS: Tenascin-C protein expression in femoral spongy bone of mice with or without osteoporosis was analyzed using Western blotting. In MC3T3-E1 osteoblasts with or without tenascin-C depletion by a specific siRNA targeting tenascin-C, alkaline phosphatase activity and Dickkopf-1 (DKK-1) expression were determined using quantitative RT-PCR and Western blotting, and the transcriptional activity of Wnt signaling pathway was analyzed using a luciferase reporter assay...
August 20, 2016: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
Anna M Piccinini, Lorena Zuliani-Alvarez, Jenny M P Lim, Kim S Midwood
Macrophages exhibit a phenotypic plasticity that enables them to orchestrate specific immune responses to distinct threats. The microbial product lipopolysaccharide (LPS) and the extracellular matrix glycoprotein tenascin-C are released during bacterial infection and tissue injury, respectively, and both activate Toll-like receptor 4 (TLR4). We found that these two TLR4 ligands stimulated distinct signaling pathways in macrophages, resulting in cells with divergent phenotypes. Although macrophages activated by LPS or tenascin-C displayed some common features, including activation of nuclear factor κB and mitogen-activated protein kinase signaling and cytokine synthesis, each ligand stimulated the production of different subsets of cytokines and generated different phosphoproteomic signatures...
2016: Science Signaling
Melissa R Andrews, Sara Soleman, Menghon Cheah, David A Tumbarello, Matthew R J Mason, Elizabeth Moloney, Joost Verhaagen, Jean-Charles Bensadoun, Bernard Schneider, Patrick Aebischer, James W Fawcett
The regenerative ability of CNS axons decreases with age, however, this ability remains largely intact in PNS axons throughout adulthood. These differences are likely to correspond with age-related silencing of proteins necessary for axon growth and elongation. In previous studies, it has been shown that reintroduction of the α9 integrin subunit (tenascin-C receptor, α9) that is downregulated in adult CNS can improve neurite outgrowth and sensory axon regeneration after a dorsal rhizotomy or a dorsal column crush spinal cord lesion...
July 2016: ENeuro
Nelson Monteiro, Elizabeth E Smith, Shantel Angstadt, Weibo Zhang, Ali Khademhosseini, Pamela C Yelick
Tissue engineering and regenerative medicine technologies offer promising therapies for both medicine and dentistry. Our long-term goal is to create functional biomimetic tooth buds for eventual tooth replacement in humans. Here, our objective was to create a biomimetic 3D tooth bud model consisting of dental epithelial (DE) - dental mesenchymal (DM) cell sheets (CSs) combined with biomimetic enamel organ and pulp organ layers created using GelMA hydrogels. Pig DE or DM cells seeded on temperature-responsive plates at various cell densities (0...
November 2016: Biomaterials
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