DOCSLIB.ORG

WISP1 Regulation by Micrornas in Pulmonary Fibrosis“

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
WISP1 Regulation by Micrornas in Pulmonary Fibrosis“ Aus dem Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten der Ludwig-Maximilians-Universität München Direktor: Prof. Dr. med. Christian Weber WISP1 Regulation by MicroRNAs in Pulmonary Fibrosis Dissertation zum Erwerb des Doktorgrades der Naturwissenschaften an der Medizinischen Fakultät der Ludwig-Maximilians-Universität München vorgelegt von Barbara Berschneider aus Regensburg 2014 Meiner Familie Gedruckt mit Genehmigung der Medizinischen Fakultät der Ludwig-Maximilians-Universität München Betreuer: PD Dr. rer. nat. Peter Neth Zweitgutachter: Prof. Dr. rer.nat. Wolfgang Zimmermann Dekan: Prof. Dr.med. Dr.h.c. Maximilian Reiser, FACR, FRCR Tag der mündlichen Prüfung: 6. November 2014 TABLE OF CONTENTS Table of Contents ........................................................................................................... I Abbreviations .............................................................................................................. VI 1 Zusammenfassung .................................................................................................. 1 2 Summary .................................................................................................................... 2 3 Introduction ............................................................................................................. 3 3.1 Idiopathic pulmonary fibrosis ............................................................................................................... 3 3.1.1 Clinical features of IPF .................................................................................................................... 3 3.1.2 Pathological features of IPF .......................................................................................................... 4 3.1.3 Pathomechanisms of IPF ............................................................................................................... 5 3.1.3.1 Genetic predispositions of pulmonary fibrosis ........................................................... 6 3.1.3.2 Key cell types in pulmonary fibrosis ................................................................................ 6 3.1.3.3 Growth factor signalling in pulmonary fibrosis .......................................................... 7 3.1.4 Animal models of lung fibrosis ................................................................................................... 9 3.1.4.1 Bleomycin model of pulmonary fibrosis ........................................................................ 9 3.1.4.2 Overexpression of TGF-β1 .................................................................................................... 9 3.2 WISP1 ............................................................................................................................................................ 10 3.2.1 WISP1 gene and protein structure ......................................................................................... 10 3.2.2 WISP1 expression .......................................................................................................................... 11 3.2.3 WISP1 function ............................................................................................................................... 12 3.2.4 WISP1 regulation ........................................................................................................................... 14 3.3 MicroRNAs .................................................................................................................................................. 15 3.3.1 MiRNA biogenesis .......................................................................................................................... 15 3.3.2 MiRNA target recognition and function ............................................................................... 17 3.3.3 MiRNAs in pulmonary fibrosis ................................................................................................. 18 3.4 Aims of this study ..................................................................................................................................... 19 I 4 Materials and Methods ....................................................................................... 20 4.1 Materials ...................................................................................................................................................... 20 4.1.1 Laboratory equipment and software .................................................................................... 20 4.1.2 Chemicals and consumables ..................................................................................................... 22 4.1.3 Buffers and solutions ................................................................................................................... 24 4.1.4 Standards and kits ......................................................................................................................... 25 4.1.5 Enzymes ............................................................................................................................................. 26 4.1.6 Plasmids ............................................................................................................................................ 27 4.1.6.1 Molecular cloning .................................................................................................................. 28 4.1.6.2 SiRNA .......................................................................................................................................... 29 4.1.6.3 Sequencing primers .............................................................................................................. 30 4.1.6.4 MiRNA – mimics and inhibitors ...................................................................................... 30 4.1.6.5 MiScript primer assays ....................................................................................................... 31 4.1.6.6 TaqMan assays ........................................................................................................................ 31 4.1.6.7 Quantitative PCR .................................................................................................................... 31 4.1.7 Antibodies ......................................................................................................................................... 33 4.1.8 Bacteria .............................................................................................................................................. 34 4.1.9 Cell lines and primary cells ....................................................................................................... 35 4.1.10 Animals ............................................................................................................................................... 36 4.1.11 Human Tissue .................................................................................................................................. 36 4.2 Methods ........................................................................................................................................................ 37 4.2.1 Animal models of pulmonary fibrosis .................................................................................. 37 4.2.1.1 Bleomycin model of pulmonary fibrosis ..................................................................... 37 4.2.1.2 Adenoviral TGF-β1-induced fibrosis ............................................................................. 37 4.2.2 Cell biology ....................................................................................................................................... 38 4.2.2.1 Primary cell isolations ......................................................................................................... 38 4.2.2.1.1 Isolation of primary alveolar type II cells .......................................................................... 38 4.2.2.1.2 Isolation of primary fibroblasts ............................................................................................. 38 4.2.2.2 Cryopreservation of mammalian cells ......................................................................... 39 4.2.2.3 Culturing and sub-culturing of mammalian cells .................................................... 39 4.2.2.4 Cell treatments ....................................................................................................................... 40 4.2.2.5 Lipotransfection of cells ..................................................................................................... 40 II 4.2.3 Microbiology .................................................................................................................................... 42 4.2.3.1 Transformation of chemically competent E. coli ..................................................... 42 4.2.3.2 Storage of E. coli ..................................................................................................................... 42 4.2.3.3 Cultivation of E. coli .............................................................................................................. 42 4.2.4 Molecular biology .......................................................................................................................... 42 4.2.4.1 Isolation of genomic DNA (gDNA) .................................................................................. 42 4.2.4.2
Load more

Recommended publications
  • The Emerging Roles of CCN3 Protein in Immune-Related Diseases
    Hindawi Mediators of Inflammation Volume 2021, Article ID 5576059, 8 pages https://doi.org/10.1155/2021/5576059 Review Article The Emerging Roles of CCN3 Protein in Immune-Related Diseases Linan Peng,1,2 Yingying Wei,3 Yijia Shao,1 Yi Li,1 Na Liu,1 and Lihua Duan 1 1Department of Rheumatology and Clinical Immunology, Jiangxi Provincial People’s Hospital Affiliated to Nanchang University, Nanchang, China 2School of Medicine, Xiamen University, Xiamen, China 3Department of Rheumatology and Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China Correspondence should be addressed to Lihua Duan; [email protected] Received 6 January 2021; Revised 24 March 2021; Accepted 29 April 2021; Published 18 May 2021 Academic Editor: Yan Yang Copyright © 2021 Linan Peng et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The CCN proteins are a family of extracellular matrix- (ECM-) associated proteins which currently consist of six secreted proteins (CCN1-6). CCN3 protein, also known as nephroblastoma overexpressed protein (NOV), is a member of the CCN family with multiple biological functions, implicated in major cellular processes such as cell growth, migration, and differentiation. Recently, CCN3 has emerged as a critical regulator in a variety of diseases, including immune-related diseases, including rheumatology arthritis, osteoarthritis, and systemic sclerosis. In this review, we will briefly introduce the structure and function of the CCN3 protein and summarize the roles of CCN3 in immune-related diseases, which is essential to understand the functions of the CCN3 in immune-related diseases.
    [Show full text]
  • Report on the 8Th International Workshop on the CCN Family of Genes – Nice November 3–8, 2015
    J. Cell Commun. Signal. (2016) 10:77–86 DOI 10.1007/s12079-016-0317-y EDITORIAL Report on the 8th international workshop on the CCN family of genes – Nice November 3–8, 2015 Bernard Perbal1 & Lester Lau 2 & Karen Lyons3 & Satoshi Kubota4 & Herman Yeger5 & Gary Fisher6 Received: 29 January 2016 /Accepted: 29 January 2016 /Published online: 26 February 2016 # The International CCN Society 2016 The 8th international workshop on the CCN family of genes was able and enthusiastic about participating with us in the full was held for a second time in Nice, from November 3rd to 8th, sessions of the meeting. It is always a unique and fruitful 2015. Under particularly sunny and warm weather everyone opportunity for all participants, either young or established enjoyed the charms of the Mediterranean coastline. scientists, to share time with the awardees. Thanks to Annick Perbal, the social events during the meet- This year we also had the pleasure to welcome Robert ing were a real success and were truly well appreciated by all. Baxter, a former ICCNS-Springer awardee, who flew in from The choice of the Westminster hotel was an excellent one. Australia to join us and present a special conference on the role of This year the ICCNS honored and warmly welcomed IGFBP3 in the breast cancer response to DNA damaging Judith Campisi, the recipient of the 2015 ICCNS-Springer therapy. award, who accepted to present a conference on senescence Those who did not have the opportunity to make it at the time and cancer. We are grateful to Judith Campisi who came a Robert Baxter received the award in Sydney, could then enjoy long way from San Francisco, despite being under the weather sharing experiences and discuss possible levels of interactions with a bad cold and sore throat.
    [Show full text]
  • And the CCN Family of Genes: Structural and Functional Issues
    J Clin Pathol: Mol Pathol 2001;54:57–79 57 Review Mol Path: first published as 10.1136/mp.54.2.57 on 1 April 2001. Downloaded from NOV (nephroblastoma overexpressed) and the CCN family of genes: structural and functional issues B Perbal Abstract terminus is expected to confer on the The CCN family of genes presently con- truncated polypeptide constitutive posi- sists of six distinct members encoding tive or negative activities. proteins that participate in fundamental (J Clin Pathol: Mol Pathol 2001;54:57–79) biological processes such as cell prolifera- tion, attachment, migration, diVerentia- Keywords: cancer; diVerentiation; signalling; develop- tion, wound healing, angiogenesis, and ment; angiogenesis; fibrosis; ctgf; cyr61; wisp; CCN several pathologies including fibrosis and tumorigenesis. Whereas CYR61 and CTGF were reported to act as positive The regulation of cellular growth, diVerentia- regulators of cell growth, NOV (nephrob- tion, and death is central to a myriad of lastoma overexpressed) provided the first biological processes that govern the appear- example of a CCN protein with negative ance, maintenance, and termination of life. regulatory properties and the first exam- Although many genes whose products are ple of aberrant expression being associ- reported to play a key role in cell growth con- ated with tumour development. The trol have been described, several basic regula- subsequent discovery of the ELM1, tory circuits involve proteins yet to be identi- rCOP1, and WISP proteins has broadened fied. http://mp.bmj.com/ The discovery of three structurally related the variety of functions attributed to the genes whose expression was modulated by CCN proteins and has extended previous growth factors and altered in cancer cells has observations to other biological systems.
    [Show full text]
  • Diseasespecific and Inflammationindependent Stromal
    Full Length Arthritis & Rheumatism DOI 10.1002/art.37704 Disease-specific and inflammation-independent stromal alterations in spondyloarthritis synovitis Nataliya Yeremenko1,2, Troy Noordenbos1,2, Tineke Cantaert1,3, Melissa van Tok1,2, Marleen van de Sande1, Juan D. Cañete4, Paul P. Tak1,5*, Dominique Baeten1,2 1Department of Clinical Immunology and Rheumatology and 2Department of Experimental Immunology, Academic Medical Center/University of Amsterdam, the Netherlands. 3Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA. 4Department of Rheumatology, Hospital Clinic de Barcelona and IDIBAPS, Spain. 5Arthrogen B.V., Amsterdam, the Netherlands. *Currently also: GlaxoSmithKline, Stevenage, U.K. Corresponding author: Dominique Baeten, MD, PhD, Department of Clinical Immunology and Rheumatology, F4-105, Academic Medical Center/University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. E-mail: [email protected] This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as an ‘Accepted Article’, doi: 10.1002/art.37704 © 2012 American College of Rheumatology Received: Apr 11, 2012; Revised: Jul 25, 2012; Accepted: Sep 06, 2012 Arthritis & Rheumatism Page 2 of 36 Abstract Objective: The molecular processes driving the distinct patterns of synovial inflammation and tissue remodelling in spondyloarthritis (SpA) versus rheumatoid arthritis (RA) remain largely unknown. Therefore, we aimed to identify novel and unsuspected disease- specific pathways in SpA by a systematic and unbiased synovial gene expression analysis. Methods: Differentially expressed genes were identified by pan-genomic microarray and confirmed by quantitative PCR and immunohistochemistry using synovial tissue biopsies of SpA (n=63), RA (n=28) and gout (n=9) patients.
    [Show full text]
  • RAPID COMMUNICATION Intrinsic Biological Activity of The
    R1 RAPID COMMUNICATION Intrinsic biological activity of the thrombospondin structural homology repeat in connective tissue growth factor Zhen-Yue Tong1,2 and David R Brigstock1–3 1Center for Cell and Vascular Biology, Children’s Research Institute, 700 Children’s Drive, Columbus, Ohio 43205, USA 2Department of Surgery and 3Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, Ohio 43212, USA (Requests for offprints should be addressed toDRBrigstockatCenter for Cell and Vascular Biology, Children’s Research Institute; Email: [email protected]) Abstract Connective tissue growth factor (CCN2) is a 349-residue was attributed to binding interactions with cell surface mosaic protein that contains four structural modules integrin 61. As assessed by RT-PCR or Western (modules 1–4), which are presumptive domains for inter- blotting, CCN23 stimulated production of fibronectin and actions with regulatory binding proteins and receptors. pro-collagen type IV(5), both of which are downstream Module 3, corresponding to residues 199–243, is a throm- components of HSC-mediated fibrogenesis and which are bospondin structural homology repeat (TSR) and is constituents of high density matrix in fibrotic lesions. flanked by regions that are highly susceptible to proteo- These data show that while the full length CCN2 protein lytic cleavage. To test whether CCN2 module 3 (CCN23) is strongly associated with fibrosis and stellate cell func- has intrinsic biological properties, it was produced recom- tion, key integrin-binding properties, signaling, and fibro- binantly in Escherichia coli (E. coli) and examined for its genic pathways are exhibited by module 3 alone. These effects on the function of hepatic stellate cells (HSC), the data indicate that module 3 of CCN2 is intrinsically active principal fibrogenic cell type in the liver.
    [Show full text]
  • 0.5) in Stat3∆/∆ Compared with Stat3flox/Flox
    Supplemental Table 2 Genes down-regulated (<0.5) in Stat3∆/∆ compared with Stat3flox/flox Probe ID Gene Symbol Gene Description Entrez gene ID 1460599_at Ermp1 endoplasmic reticulum metallopeptidase 1 226090 1460463_at H60c histocompatibility 60c 670558 1460431_at Gcnt1 glucosaminyl (N-acetyl) transferase 1, core 2 14537 1459979_x_at Zfp68 zinc finger protein 68 24135 1459747_at --- --- --- 1459608_at --- --- --- 1459168_at --- --- --- 1458718_at --- --- --- 1458618_at --- --- --- 1458466_at Ctsa cathepsin A 19025 1458345_s_at Colec11 collectin sub-family member 11 71693 1458046_at --- --- --- 1457769_at H60a histocompatibility 60a 15101 1457680_a_at Tmem69 transmembrane protein 69 230657 1457644_s_at Cxcl1 chemokine (C-X-C motif) ligand 1 14825 1457639_at Atp6v1h ATPase, H+ transporting, lysosomal V1 subunit H 108664 1457260_at 5730409E04Rik RIKEN cDNA 5730409E04Rik gene 230757 1457070_at --- --- --- 1456893_at --- --- --- 1456823_at Gm70 predicted gene 70 210762 1456671_at Tbrg3 transforming growth factor beta regulated gene 3 21378 1456211_at Nlrp10 NLR family, pyrin domain containing 10 244202 1455881_at Ier5l immediate early response 5-like 72500 1455576_at Rinl Ras and Rab interactor-like 320435 1455304_at Unc13c unc-13 homolog C (C. elegans) 208898 1455241_at BC037703 cDNA sequence BC037703 242125 1454866_s_at Clic6 chloride intracellular channel 6 209195 1453906_at Med13l mediator complex subunit 13-like 76199 1453522_at 6530401N04Rik RIKEN cDNA 6530401N04 gene 328092 1453354_at Gm11602 predicted gene 11602 100380944 1453234_at
    [Show full text]
  • Long, Noncoding RNA Dysregulation in Glioblastoma
    cancers Review Long, Noncoding RNA Dysregulation in Glioblastoma Patrick A. DeSouza 1,2 , Xuan Qu 1, Hao Chen 1,3, Bhuvic Patel 1 , Christopher A. Maher 2,4,5,6 and Albert H. Kim 1,6,* 1 Department of Neurological Surgery, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA; [email protected] (P.A.D.); [email protected] (X.Q.); [email protected] (H.C.); [email protected] (B.P.) 2 Department of Internal Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA; [email protected] 3 Department of Neuroscience, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA 4 Department of Biomedical Engineering, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA 5 McDonnell Genome Institute, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA 6 Siteman Cancer Center, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA * Correspondence: [email protected] Simple Summary: Developing effective therapies for glioblastoma (GBM), the most common primary brain cancer, remains challenging due to the heterogeneity within tumors and therapeutic resistance that drives recurrence. Noncoding RNAs are transcribed from a large proportion of the genome and remain largely unexplored in their contribution to the evolution of GBM tumors. Here, we will review the general mechanisms of long, noncoding RNAs and the current knowledge of how these impact heterogeneity and therapeutic resistance in GBM. A better understanding of the molecular drivers required for these aggressive tumors is necessary to improve the management and outcomes Citation: DeSouza, P.A.; Qu, X.; of this challenging disease.
    [Show full text]
  • Product Description SALSA MLPA Probemix P476-A1 ZNRF3
    MRC-Holland ® Product Description version A1-02; Issued 25 September 2018 MLPA Product Description SALSA ® MLPA ® Probemix P476-A1 ZNRF3 To be used with the MLPA General Protocol. Version A1. New Product. Catalogue numbers: • P476-025R: SALSA MLPA Probemix P476 ZNRF3, 25 reactions. • P476-050R: SALSA MLPA Probemix P476 ZNRF3, 50 reactions. • P476-100R: SALSA MLPA Probemix P476 ZNRF3, 100 reactions. To be used in combination with a SALSA MLPA reagent kit, available for various number of reactions. MLPA reagent kits are either provided with FAM or Cy5.0 dye-labelled PCR primer, suitable for Applied Biosystems and Beckman capillary sequencers, respectively (see www.mlpa.com ). Certificate of Analysis: Information regarding storage conditions, quality tests, and a sample electropherogram from the current sales lot is available at www.mlpa.com . Precautions and warnings: For professional use only. Always consult the most recent product description AND the MLPA General Protocol before use: www.mlpa.com . It is the responsibility of the user to be aware of the latest scientific knowledge of the application before drawing any conclusions from findings generated with this product. General information: The SALSA MLPA Probemix P476 ZNRF3 is a research use only (RUO) assay for the detection of deletions and duplications in the ZNRF3 gene. ZNRF3 is an E3 ubiquitin-protein ligase that acts as a negative feedback regulator of Wnt signalling (Hao et al. 2012). Three independent studies show homozygous deletions of the ZNRF3 gene in 10 to 16% of adrenocortical carcinoma cases (Assié et al. 2014; Juhlin et al. 2015; Zheng et al. 2016). Moreover, in 51% of microsatellite stable colorectal cancers deletion events at the ZNRF3 locus are detected (Bond et al.
    [Show full text]
  • Identification of Active Signaling Pathways by Integrating Gene Expression and Protein Interaction Data Md Humayun Kabir1,2,3, Ralph Patrick2,4,5, Joshua W
    Kabir et al. BMC Systems Biology 2018, 12(Suppl 9):120 https://doi.org/10.1186/s12918-018-0655-x RESEARCH Open Access Identification of active signaling pathways by integrating gene expression and protein interaction data Md Humayun Kabir1,2,3, Ralph Patrick2,4,5, Joshua W. K. Ho2,4,6* and Michael D. O’Connor1,7* From 29th International Conference on Genome Informatics Yunnan, China. 3-5 December 2018 Abstract Background: Signaling pathways are the key biological mechanisms that transduce extracellular signals to affect transcription factor mediated gene regulation within cells. A number of computational methods have been developed to identify the topological structure of a specific signaling pathway using protein-protein interaction data, but they are not designed for identifying active signaling pathways in an unbiased manner. On the other hand, there are statistical methods based on gene sets or pathway data that can prioritize likely active signaling pathways, but they do not make full use of active pathway structure that link receptor, kinases and downstream transcription factors. Results: Here, we present a method to simultaneously predict the set of active signaling pathways, together with their pathway structure, by integrating protein-protein interaction network and gene expression data. We evaluated the capacity for our method to predict active signaling pathways for dental epithelial cells, ocular lens epithelial cells, human pluripotent stem cell-derived lens epithelial cells, and lens fiber cells. This analysis showed our approach could identify all the known active pathways that are associated with tooth formation and lens development. Conclusions: The results suggest that SPAGI can be a useful approach to identify the potential active signaling pathways given a gene expression profile.
    [Show full text]
  • Biological Characteristics of CCN Proteins in Tumor Development Stephany C
    CCN proteins in tumor development JBUON 2016; 21(6): 1359-1367 ISSN: 1107-0625, online ISSN: 2241-6293 • www.jbuon.com E-mail: [email protected] REVIEW ARTICLE Biological characteristics of CCN proteins in tumor development Stephany C. Barreto, Amitabha Ray, Page AG. Edgar Saint James School of Medicine, Anguilla, British West Indies Summary The extracellular matrix (ECM) is no longer regarded as teins are capable of modulating a variety of biological pro- inert, rather it has multiple versatile physiologic functions. cesses in health as well as in disease conditions. In tumor Its diverse composition is implicated in each step of cancer development and in tumor microenvironment, CCN proteins progression including inflammation, angiogenesis, tumor can influence multiple facets of pathophysiological process- invasion and metastasis. In addition to structural proteins, es including cellular proliferation, invasion and metastasis. the ECM also contains a family of non-structural proteins This review has attempted a cohesive look at the CCN family called matricellular proteins. The six secreted CCN proteins, protein functions in a tumor-specific manner. which belong to the matricellular protein family, include the following: Cyr61 (CCN1), CTGF (CCN2), Nov (CCN3), WISP- Key words: cancer, CCN proteins, cell signaling, extracel- 1 (CCN4), WISP-2 (CCN5) and WISP-3(CCN6). These pro- lular matrix, matricellular proteins Introduction The extracellular matrix (ECM) consists of or CCN1), connective tissue growth factor (CTGF diverse groups of proteins including matricellu- or CCN2), nephroblastoma overexpressed protein lar proteins, which are a family of non-structural (Nov or CCN3), Wnt-inducible secreted protein-1 matrix proteins capable of modulating a variety (WISP-1 or CCN4), WISP-2 (CCN5) and WISP- of biological processes.
    [Show full text]
  • Modulation of Connective Tissue Growth Factor and Activin Receptor 2B Function in Cardiac Hypertrophy and Fibrosis
    D 1526 OULU 2019 D 1526 UNIVERSITY OF OULU P.O. Box 8000 FI-90014 UNIVERSITY OF OULU FINLAND ACTA UNIVERSITATIS OULUENSIS ACTA UNIVERSITATIS OULUENSIS ACTA DMEDICA Zoltan Szabo Zoltan Szabo University Lecturer Tuomo Glumoff MODULATION OF University Lecturer Santeri Palviainen CONNECTIVE TISSUE Senior research fellow Jari Juuti GROWTH FACTOR AND ACTIVIN RECEPTOR 2B Professor Olli Vuolteenaho FUNCTION IN CARDIAC University Lecturer Veli-Matti Ulvinen HYPERTROPHY AND FIBROSIS Planning Director Pertti Tikkanen Professor Jari Juga University Lecturer Anu Soikkeli Professor Olli Vuolteenaho UNIVERSITY OF OULU GRADUATE SCHOOL; UNIVERSITY OF OULU, FACULTY OF MEDICINE; Publications Editor Kirsti Nurkkala BIOCENTER OULU ISBN 978-952-62-2339-1 (Paperback) ISBN 978-952-62-2340-7 (PDF) ISSN 0355-3221 (Print) ISSN 1796-2234 (Online) ACTA UNIVERSITATIS OULUENSIS D Medica 1526 ZOLTAN SZABO MODULATION OF CONNECTIVE TISSUE GROWTH FACTOR AND ACTIVIN RECEPTOR 2B FUNCTION IN CARDIAC HYPERTROPHY AND FIBROSIS Academic dissertation to be presented with the assent of the Doctoral Training Committee of Health and Biosciences of the University of Oulu for public defence in the Leena Palotie auditorium (101A) of the Faculty of Medicine (Aapistie 5 A), on 27 September 2019, at 13 p.m. UNIVERSITY OF OULU, OULU 2019 Copyright © 2019 Acta Univ. Oul. D 1526, 2019 Supervised by Professor Risto Kerkelä Doctor Johanna Magga Reviewed by Professor Marjukka Myllärniemi Professor Eero Mervaala Opponent Professor Antti Saraste ISBN 978-952-62-2339-1 (Paperback) ISBN 978-952-62-2340-7 (PDF) ISSN 0355-3221 (Printed) ISSN 1796-2234 (Online) Cover Design Raimo Ahonen JUVENES PRINT TAMPERE 2019 Szabo, Zoltan, Modulation of connective tissue growth factor and activin receptor 2b function in cardiac hypertrophy and fibrosis.
    [Show full text]
  • Role of the CCN Protein Family in Cancer
    BMB Rep. 2018; 51(10): 486-492 BMB www.bmbreports.org Reports Invited Mini Review Role of the CCN protein family in cancer Hyungjoo Kim1, Seogho Son1 & Incheol Shin1,2,* 1Department of Life Science, Hanyang University, Seoul 04763, 2Natural Science Institute, Hanyang University, Seoul 04763, Korea The CCN protein family is composed of six matricellular potential as therapeutic targets (3). proteins, which serve regulatory roles rather than structural The CCN protein family consists of six members: roles in the extracellular matrix. First identified as secreted cysteine-rich angiogenic inducer 61 (Cyr 61; CCN1), connective proteins which are induced by oncogenes, the acronym CCN tissue growth factor (CTGF; CCN2), nephroblastoma over- came from the names of the first three members: CYR61, expressed (NOV; CCN3), and WNT-inducible signaling CTGF, and NOV. All six members of the CCN family consist pathway protein 1, 2, and 3 (WISP 1, 2 and 3; CCN4, 5 and of four cysteine-rich modular domains. CCN proteins are 6). The first three members, Cyr 61, CTGF, and NOV, which known to regulate cell adhesion, proliferation, differentiation, gave a name and acronym to the family, were first identified as and apoptosis. In addition, CCN proteins are associated with immediate early gene products of growth factors or tumor cardiovascular and skeletal development, injury repair, in- transformation related genes (4-6). The six members of the flammation, and cancer. They function either through binding CCN protein family, except for CCN5 which lacks the to integrin receptors or by regulating the expression and cysteine-knot (CT) motif, share four conserved protein motifs: activity of growth factors and cytokines.
    [Show full text]