DOCSLIB.ORG

Matrix Metalloproteinase-11 Promotes Mouse Mammary Gland Tumor Progression Bing Tan

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Matrix Metalloproteinase-11 Promotes Mouse Mammary Gland Tumor Progression Bing Tan Matrix metalloproteinase-11 promotes mouse mammary gland tumor progression Bing Tan To cite this version: Bing Tan. Matrix metalloproteinase-11 promotes mouse mammary gland tumor progression. Ge- nomics [q-bio.GN]. Université de Strasbourg, 2018. English. NNT : 2018STRAJ047. tel-02870898 HAL Id: tel-02870898 https://tel.archives-ouvertes.fr/tel-02870898 Submitted on 17 Jun 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. UNIVERSITÉ DE STRASBOURG ÉCOLE DOCTORALE DES SCIENCES DE LA VIE ET DE LA SANTÉ Thèse présentée par Bing TAN Pour obtenir le grade de Docteur de l’Université de Strasbourg Sciences du Vivant Aspects Moléculaires et Cellulaires de la Biologie La métalloprotéase matricielle-11 facilite la progression des tumeurs de la glande mammaire murine Matrix metalloproteinase-11 promotes mouse mammary gland tumor progression Soutenue publiquement le 13 septembre 2018 Devant le jury composé de: Examinateur: Madame le Docteur Isabelle GRILLIER-VUISSOZ Rapporteurs Externe: Madame le Docteur Emmanuelle LIAUDET-COOPMAN Monsieur le Docteur Stéphane DEDIEU Rapporteur Interne: Monsieur le Docteur Olivier LEFEBVRE Directeur de Thèse: Madame le Docteur Catherine-Laure TOMASETTO Acknowledgements The completion of my PhD thesis is attributed to many people’s support. First, I want to extend my heartfelt gratitude to my supervisor Dr. Catherine-Laure TOMASETTO, whose patient guidance, constant encouragement and valuable suggestions make me successfully complete this thesis. Her modest, open-minded personality and conscientious academic spirit will inspire me in future study. If without her help in daily life, I can’t imagine what my four years in France would be like! Second, I would give my greatest thanks to Dr. Nassim DALI-YOUCEF, he not only provided lots of guidance in my research, but also answered my questions extremely patient. I would like to say many thanks to Dr. Fabien ALPY for his good suggestions and technical help in my research, especially how to analysis my data. My thanks go to the laboratory members for their help, including Dr. Marie- Christine RIO, we spent and enjoyed a very pleasure time; my thanks go to the IGBMC animal facility, ICS histopathology service and CBI image center; and my thanks go to the friends and the people whose name are not mentioned but give me a lot of help during my study, etc. Thanks for the jury members Docteur Emmanuelle LIAUDET-COOPMAN, Docteur Stéphane DEDIEU, Docteur Isabelle GRILLIER-VUISSOZ and Docteur Olivier LEFEBVRE. I would give my special thanks to my parents, my brother, my girlfriend, and my uncle Jinxiang TAN for their support. Last, acknowledgements give to La Ligue Contre Le Cancer and China Scholarship Council for provide me the scientific fundings. THANK YOU ALL MERCI À TOUTES/TOUS i Table of Contents Acknowledgements……………………………...…………………………………….i Table of Contents..………………………….….……………………………….……ii List of Figures and Tables…….….……………………….…………………..…...viii List of Abbreviations……..………………………………………………..…..….….x Summary………...………………………………………………….………...……....1 CHAPTER 1 Introduction and Review……………………………………….…..2 1.1 MMPs family…………………………………...…………………….…………..2 1.1.1 MMPs classification…………………………………………….…………..2 1.1.1.1 Collagenases……………………………………….…………………4 1.1.1.2 Gelatinases……………………………………….…………………..4 1.1.1.3 Stromelysins………………………………………………………….4 1.1.1.4 Matrilysins……………………………………………………………5 1.1.1.5 MT-MMPs………………………………...………………………….5 1.1.1.6 Other MMPs………………………………………………………….5 1.1.2 MMPs structures……………..……………………………………….…….6 1.1.3 MMPs substrates……………………………………………………………7 1.1.4 Regulation of MMPs………………………………………………………11 1.1.4.1 The expression of MMPs genes…………………………………….11 1.1.4.2 The MMPs compartmentalization…………………………………..12 1.1.4.3 The activation of pro-MMPs………………………………………..12 1.1.4.4 The inhibition of MMPs…………………………………………….14 1.1.5 Biological functions of MMPs………………………………………….....15 1.1.5.1 MMPs and mouse mammary gland development…………………..15 1.1.5.2 MMPs trigger bone growth…………………………………………18 1.1.5.3 MMPs in wound healing and cell migration………………………..19 1.1.5.4 MMPs and vascular development…………………………………..20 1.1.5.5 MMPs and immune response……………………………………….21 1.1.5.6 MMPs associate with adipogenesis and body metabolism…………22 1.1.5.7 MMPs functions from mutant mice………………………………...23 1.1.6 MMPs and cancer………………………………………………………….27 1.1.6.1 MMPs in cancer cell proliferation………………………………..…27 ii 1.1.6.2 MMPs in cancer cell apoptosis……………………………………...28 1.1.6.3 MMPs in cancer angiogenesis………………………………………29 1.1.6.4 MMPs in cancer lymphangiogenesis…………………………….….31 1.1.6.5 MMPs in cancer epithelial to mesenchymal transition……………..32 1.1.6.6 MMPs in cancer migration………………………………………….32 1.1.6.7 MMPs in cancer invasion and metastasis…………………………...34 1.1.6.8 MMPs in cancer immune surveillance…………………………...…37 1.1.6.9 MMPs have nonproteolytic functions………………………………40 1.2 MMP-11………………………………………………………………………….43 1.2.1 MMP-11 discovery………………………………………………………...43 1.2.2 MMP-11 genomic organization…………………………………………...43 1.2.3 MMP-11 protein structure…………………………………………………45 1.2.4 MMP-11 crystal structure………………………………………………….45 1.2.5 MMP-11 secretion and activation…………………………………………46 1.2.6 MMP-11 nature and recombinant protein…………………………………47 1.2.7 MMP-11 substrates………………………………………………………..47 1.2.8 MMP-11 is a paracrine factor………………………………………….…..48 1.2.9 MMP-11 physiological functions………………………………….………49 1.2.9.1 MMP-11 and embryonic development……………………………...49 1.2.9.2 MMP-11 and mammary gland involution…………………………..50 1.2.9.3 MMP-11 and adipogenesis………………………………………….51 1.2.10 MMP-11 pathological functions………………………………………….53 1.2.10.1 MMP-11 and cancer……………………………………………….53 1.2.10.1.1 MMP-11 and breast cancer…………………………………53 1.2.10.1.2 MMP-11 and other cancers…………………………………55 1.2.10.2 MMP-11 and other diseases……………………………………….57 1.2.11 The summary of MMP-11 functions……………………………………..58 1.3 Adipocytes are involved in mammary gland tumor progression………..…...60 1.3.1 Cancer-associated adipocytes……………………………………………...60 1.3.2 Adipokines………………………………………………………………...61 1.3.3 Inflammation………………………………………………………………62 1.3.4 Sex hormones……………………………………………………………...62 1.3.5 Insulin signalling and IGF-I axis…………………………………………..63 iii 1.3.6 Lipid metabolism………………………………………………….…….....63 1.4 Thesis project………………………...………………………………………….65 CHAPTER 2 Results……………………………………………………………...69 Part I The impact of MMP-11 on MMTV-PyMT mouse breast cancer progression…………………………………………………………………………..69 2.1.1 Identification of the GOF and LOF mice genotypes………………………69 2.1.2 MMP-11 decreases MMTV-PyMT mice body weight……………………70 2.1.3 MMP-11 promotes MMTV-PyMT mice mammary tumor growth……….71 2.1.4 MMP-11 plays anti-necrosis and anti-apoptotic roles in MMTV-PyMT mice at early stage of mammary tumor development…………………………...73 2.1.5 MMP-11 plays a proliferative role at early stage of tumor development in MMTV-PyMT mice and induces the insulin-like growth factor-1 signalling pathway……………………………………………………………………….…74 2.1.6 MMP-11 increased lipid uptake and utilization and promotes metabolic switch……………………………………………………………………………76 2.1.7 MMP-11 increases endoplasmic reticulum stress response and alters mitochondrial unfolded protein response………………………………………..78 2.1.8 MMP-11 promotes MMTV-PyMT mice mammary tumor stroma fibrosis at limited time points…………………………………………………………….…81 2.1.9 MMP-11 does not modulate mammary tumor angiogenesis and EMT in MMTV-PyMT mice……………………………………………………………..83 2.1.10 MMP-11 reduces dissemination of mammary tumor to the lung in MMTV- PyMT mice………………………………………………………………………84 Research article: Matrix metalloproteinase-11 promotes mouse mammary gland tumor progression. Tan et al., in preparation Part II The impact of MMP-11 overexpression restricted to adipocytes on mammary gland tumorigenesis………………………………………...…………..86 2.2.1 Generation of aP2-mMMP11-IRES-GFP-polyA construct……………….86 2.2.1.1 Amplification of IRES-GFP sequence by PCR……………………..87 2.2.1.2 To obtain the same cutting ends of IRES-GFP and aP2-mMMP11- polyA………………………………………………………………………..88 2.2.1.3 Ligation of IRES-GFP and aP2-mMMP11-polyA………………….88 2.2.1.4 Validation of aP2-mMMP11-IRES-GFP-polyA plasmid in vitro…..89 iv 2.2.1.5 Linearization of aP2-mMMP11-IRES-GFP-polyA plasmid………..90 2.2.2 Characterization of aP2-mMMP11-IRES-GFP-polyA transgenic mice lines……………………………………………………………………………...91 2.2.2.1 Verification of germline transmission of aP2-mMMP11-IRES-GFP- polyA transgenic mice lines………………………………………………...91 2.2.2.2 Verification of MMP-11 and GFP expression of the aP2-mMMP11- IRES-GFP-polyA # 18 transgenic line……………………………………...92 2.2.3 Adipocyte-specific MMP-11 promotes E0771 mouse breast tumor growth……………………………………………………………………………94 Part III The impact of ITPP on MMTV-PyMT mouse breast cancer progression…………………………………………………………………………..96 2.3.1 ITPP promotes mammary gland hyperplasia and tumor incidence………..96 2.3.2 ITPP did not promoted mammary tumor metastasis to lung………………97 CHAPTER 3 Conclusions, Discussion and Perspectives……………………….99 Part I……………………………………………...……………………………….....99 3.1.1 MMP-11 promotes mammary tumor
Load more

Recommended publications
  • Role of Cyclosporine in Gingival Hyperplasia: an in Vitro Study on Gingival Fibroblasts
    International Journal of Molecular Sciences Article Role of Cyclosporine in Gingival Hyperplasia: An In Vitro Study on Gingival Fibroblasts 1, , 2, 3 3 Dorina Lauritano * y , Annalisa Palmieri y, Alberta Lucchese , Dario Di Stasio , Giulia Moreo 1 and Francesco Carinci 4 1 Department of Medicine and Surgery, Centre of Neuroscience of Milan, University of Milano-Bicocca, 20126 Milan, Italy; [email protected] 2 Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, via Belmoro 8, 40126 Bologna, Italy; [email protected] 3 Multidisciplinary Department of Medical and Dental Specialties, University of Campania-Luigi Vanvitelli, 80138 Naples, Italy; [email protected] (A.L.); [email protected] (D.D.S.) 4 Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy; [email protected] * Correspondence: [email protected]; Tel.: +39-335-679-0163 These authors contributed equally to this work. y Received: 25 November 2019; Accepted: 13 January 2020; Published: 16 January 2020 Abstract: Background: Gingival hyperplasia could occur after the administration of cyclosporine A. Up to 90% of the patients submitted to immunosuppressant drugs have been reported to suffer from this side effect. The role of fibroblasts in gingival hyperplasia has been widely discussed by literature, showing contrasting results. In order to demonstrate the effect of cyclosporine A on the extracellular matrix component of fibroblasts, we investigated the gene expression profile of human fibroblasts after cyclosporine A administration. Materials and methods: Primary gingival fibroblasts were stimulated with 1000 ng/mL cyclosporine A solution for 16 h. Gene expression levels of 57 genes belonging to the “Extracellular Matrix and Adhesion Molecules” pathway were analyzed using real-time PCR in treated cells, compared to untreated cells used as control.
    [Show full text]
  • Intestinal Tumorigenesis Is Suppressed in Mice Lacking the Metalloproteinase Matrilysin (Knockout͞min͞colon Cancer͞extracellular Matrix͞apc)
    Proc. Natl. Acad. Sci. USA Vol. 94, pp. 1402–1407, February 1997 Medical Sciences Intestinal tumorigenesis is suppressed in mice lacking the metalloproteinase matrilysin (knockoutyMinycolon canceryextracellular matrixyAPC) CAROLE L. WILSON*†,KATHLEEN J. HEPPNER*†,PATRICIA A. LABOSKY*‡,BRIGID L. M. HOGAN*‡, AND LYNN M. MATRISIAN*§ *Department of Cell Biology and ‡Howard Hughes Medical Institute, Vanderbilt University, Nashville, TN 37232 Communicated by Ruth Sager, Dana–Farber Cancer Institute, Boston, MA, December 12, 1996 (received for review June 27, 1996) ABSTRACT Matrix metalloproteinases (MMPs) classi- The Min (multiple intestinal neoplasia) mouse has proven to cally have been implicated in basement membrane destruction be a powerful model system to study molecules involved in the associated with late-stage tumor cell invasion and metastasis. progression of intestinal adenomas. It has been determined However, recent studies have demonstrated that one MMP that a nonsense autosomal dominant germline mutation in the family member, matrilysin, is expressed in a high percentage adenomatous polyposis coli (Apc) gene (the ApcMin allele) of early-stage human colorectal tumors. We analyzed matri- induces spontaneous intestinal tumors in these mice, providing lysin expression in benign intestinal tumors from mice het- a model that closely mimics the human hereditary colon cancer erozygous for the ApcMin allele (Miny1) and found that the syndrome, familial adenomatous polyposis (13, 14). Congenic mRNA was induced in the majority (88%) of these adenomas. C57BLy6-Min mice heterozygous for this mutant allele Protein was detected in the tumor cells, where, surprisingly, (Miny1) develop numerous benign tumors throughout the it was predominantly immunolocalized to the lumenal surface intestinal tract, although with less frequency in the large bowel, of dysplastic glands rather than the basement membrane or and have an average life span of 119 days (13, 15).
    [Show full text]
  • 2335 Roles of Molecules Involved in Epithelial/Mesenchymal Transition
    [Frontiers in Bioscience 13, 2335-2355, January 1, 2008] Roles of molecules involved in epithelial/mesenchymal transition during angiogenesis Giulio Ghersi Dipartimento di Biologia Cellulare e dello Sviluppo, Universita di Palermo, Italy TABLE OF CONTENTS 1. Abstract 2. Introduction 3. Extracellular matrix 3.1. ECM and integrins 3.2. Basal lamina components 4. Cadherins. 4.1. Cadherins in angiogenesis 5. Integrins. 5.1. Integrins in angiogenesis 6. Focal adhesion molecules 7. Proteolytic enzymes 7.1. Proteolytic enzymes inhibitors 7.2. Proteolytic enzymes in angiogenesis 8. Perspective 9. Acknowledgements 10. References 1.ABSTRACT 2. INTRODUCTION Formation of vessels requires “epithelial- Growth of new blood vessels (angiogenesis) mesenchymal” transition of endothelial cells, with several plays a key role in several physiological processes, such modifications at the level of endothelial cell plasma as vascular remodeling during embryogenesis and membranes. These processes are associated with wound healing tissue repair in the adult; as well as redistribution of cell-cell and cell-substrate adhesion pathological processes, including rheumatoid arthritis, molecules, cross talk between external ECM and internal diabetic retinopathy, psoriasis, hemangiomas, and cytoskeleton through focal adhesion molecules and the cancer (1). Vessel formation entails the “epithelial- expression of several proteolytic enzymes, including matrix mesenchymal” transition of endothelial cells (ECs) “in metalloproteases and serine proteases. These enzymes with vivo”; a similar phenotypic exchange can be induced “in their degradative action on ECM components, generate vitro” by growing ECs to low cell density, or in “wound molecules acting as activators and/or inhibitors of healing” experiments or perturbing cell adhesion and angiogenesis. The purpose of this review is to provide an associated molecule functions.
    [Show full text]
  • A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
    Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated.
    [Show full text]
  • Smooth Muscle-Specific MMP17 (MT4-MMP) Defines the Intestinal ECM Niche 2 3 Mara Martín-Alonso1*, Håvard T
    bioRxiv preprint doi: https://doi.org/10.1101/2020.06.18.147769; this version posted June 18, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 Smooth muscle-specific MMP17 (MT4-MMP) defines the intestinal ECM niche 2 3 Mara Martín-Alonso1*, Håvard T. Lindholm1,# , Sharif Iqbal2,3,#, Pia Vornewald1#, Sigrid Hoel1, 4 Mirjam J. Damen4, A.F.Maarten Altelaar4, Pekka Katajisto2,3,5, Alicia G. Arroyo6,7, Menno J. 5 Oudhoff1* 6 7 1CEMIR – Centre of Molecular Inflammation Research, Department of Clinical and Molecular 8 Medicine, NTNU – Norwegian University of Science and Technology, 7491 Trondheim, 9 Norway 10 2Institute of Biotechnology, HiLIFE, University of Helsinki, Finland 11 3Molecular and Integrative Bioscience Research Programme, Faculty of Biological and 12 Environmental Sciences, University of Helsinki, Helsinki, Finland 13 4Biomolecular Mass Spectrometry and Proteomics, Utrecht University, Utrecht, The 14 Netherlands 15 5Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden 16 6Centro de Investigaciones Biológicas Margarita Salas (CIB-CSIC), Madrid, Spain 17 7Vascular Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares 18 (CNIC), Madrid, Spain.CNIC, Madrid, Spain 19 20 #These authors contributed equally to this work 21 *corresponding authors, e-mail: [email protected], [email protected] 22 bioRxiv preprint doi: https://doi.org/10.1101/2020.06.18.147769; this version posted June 18, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.
    [Show full text]
  • On and Polymorphisms in Q Fever
    Matrix metalloproteinase expression, produc3on and polymorphisms in Q fever Anne F.M. Jansen1,2, Teske Schoffelen1,2, Julien Textoris3, Jean Louis Mege3, Chantal P. Bleeker-Rovers1,2, Esther van de Vosse4, Hendrik Jan Roest5, Marcel van Deuren1,2 1. Department of Internal Medicine, Division of Experimental Medicine, Radboud university medical center, Nijmegen, The Netherlands 2. Radboud Expert Centre for Q fever, Radboud university medical center, Nijmegen, the Netherlands, 3. URMITE, CNRS UMR 7278, IRD 198, INSERM 1095 Aix-Marseille University, Marseille, France 4. Department of Infec3ous Diseases, Leiden University Medical Center, Leiden, The Netherlands 5. Department of Bacteriology and TSEs, Central Veterinary Instute, part of Wageningen UR, Lelystad, the Netherlands Background C. burnei induces MMP-1 and MMP-9 produc3on in PBMCs Chronic Q fever is a life threatening condi3on caused by the Gram-negave bacterium Coxiella burnei, manifes3ng as an infec3on of aneurysms, aor3c prosthesis or heart valves. Matrix metalloproteinases (MMPs) are proteoly3c enzymes that cleave extracellular matrix and are implicated in the pathology of aneurysms and endocardi3s. Currently, the contribu3on of MMPs to the pathogenesis of chronic Q fever is unknown. Methods We inves3gated the C. burnei specific gene expression of MMPs in PBMCs and protein produc3on by ELISA in chronic Q fever paents (n=6, n=10, respec3vely), cardiovascular paents with a history of Q fever (n=10) and healthy controls (n=4, n=10, respec3vely), in some experiments, the controls had vascular disease (n=10). Circulang MMP levels were assessed with Luminex technology and these groups were also genotyped for 20 SNPs in MMP and Tissue Inhibitor of MMP (TIMP) genes.
    [Show full text]
  • Gene Symbol Category ACAN ECM ADAM10 ECM Remodeling-Related ADAM11 ECM Remodeling-Related ADAM12 ECM Remodeling-Related ADAM15 E
    Supplementary Material (ESI) for Integrative Biology This journal is (c) The Royal Society of Chemistry 2010 Gene symbol Category ACAN ECM ADAM10 ECM remodeling-related ADAM11 ECM remodeling-related ADAM12 ECM remodeling-related ADAM15 ECM remodeling-related ADAM17 ECM remodeling-related ADAM18 ECM remodeling-related ADAM19 ECM remodeling-related ADAM2 ECM remodeling-related ADAM20 ECM remodeling-related ADAM21 ECM remodeling-related ADAM22 ECM remodeling-related ADAM23 ECM remodeling-related ADAM28 ECM remodeling-related ADAM29 ECM remodeling-related ADAM3 ECM remodeling-related ADAM30 ECM remodeling-related ADAM5 ECM remodeling-related ADAM7 ECM remodeling-related ADAM8 ECM remodeling-related ADAM9 ECM remodeling-related ADAMTS1 ECM remodeling-related ADAMTS10 ECM remodeling-related ADAMTS12 ECM remodeling-related ADAMTS13 ECM remodeling-related ADAMTS14 ECM remodeling-related ADAMTS15 ECM remodeling-related ADAMTS16 ECM remodeling-related ADAMTS17 ECM remodeling-related ADAMTS18 ECM remodeling-related ADAMTS19 ECM remodeling-related ADAMTS2 ECM remodeling-related ADAMTS20 ECM remodeling-related ADAMTS3 ECM remodeling-related ADAMTS4 ECM remodeling-related ADAMTS5 ECM remodeling-related ADAMTS6 ECM remodeling-related ADAMTS7 ECM remodeling-related ADAMTS8 ECM remodeling-related ADAMTS9 ECM remodeling-related ADAMTSL1 ECM remodeling-related ADAMTSL2 ECM remodeling-related ADAMTSL3 ECM remodeling-related ADAMTSL4 ECM remodeling-related ADAMTSL5 ECM remodeling-related AGRIN ECM ALCAM Cell-cell adhesion ANGPT1 Soluble factors and receptors
    [Show full text]
  • Investigation of the Underlying Hub Genes and Molexular Pathogensis in Gastric Cancer by Integrated Bioinformatic Analyses
    bioRxiv preprint doi: https://doi.org/10.1101/2020.12.20.423656; this version posted December 22, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Investigation of the underlying hub genes and molexular pathogensis in gastric cancer by integrated bioinformatic analyses Basavaraj Vastrad1, Chanabasayya Vastrad*2 1. Department of Biochemistry, Basaveshwar College of Pharmacy, Gadag, Karnataka 582103, India. 2. Biostatistics and Bioinformatics, Chanabasava Nilaya, Bharthinagar, Dharwad 580001, Karanataka, India. * Chanabasayya Vastrad [email protected] Ph: +919480073398 Chanabasava Nilaya, Bharthinagar, Dharwad 580001 , Karanataka, India bioRxiv preprint doi: https://doi.org/10.1101/2020.12.20.423656; this version posted December 22, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract The high mortality rate of gastric cancer (GC) is in part due to the absence of initial disclosure of its biomarkers. The recognition of important genes associated in GC is therefore recommended to advance clinical prognosis, diagnosis and and treatment outcomes. The current investigation used the microarray dataset GSE113255 RNA seq data from the Gene Expression Omnibus database to diagnose differentially expressed genes (DEGs). Pathway and gene ontology enrichment analyses were performed, and a proteinprotein interaction network, modules, target genes - miRNA regulatory network and target genes - TF regulatory network were constructed and analyzed. Finally, validation of hub genes was performed. The 1008 DEGs identified consisted of 505 up regulated genes and 503 down regulated genes.
    [Show full text]
  • Effect of Nanoparticles on the Expression and Activity of Matrix Metalloproteinases
    Nanotechnol Rev 2018; 7(6): 541–553 Review Magdalena Matysiak-Kucharek*, Magdalena Czajka, Krzysztof Sawicki, Marcin Kruszewski and Lucyna Kapka-Skrzypczak Effect of nanoparticles on the expression and activity of matrix metalloproteinases https://doi.org/10.1515/ntrev-2018-0110 Received September 14, 2018; accepted October 11, 2018; previously 1 Introduction published online November 15, 2018 Matrix metallopeptidases, commonly known as matrix Abstract: Matrix metallopeptidases, commonly known metalloproteinases (MMPs), are zinc-dependent proteo- as matrix metalloproteinases (MMPs), are a group of pro- lytic enzymes whose primary function is the degradation teolytic enzymes whose main function is the remodeling and remodeling of extracellular matrix (ECM) compo- of the extracellular matrix. Changes in the activity of nents. ECM is a complex, dynamic structure that condi- these enzymes are observed in many pathological states, tions the proper tissue architecture. MMPs by digesting including cancer metastases. An increasing body of evi- ECM proteins eliminate structural barriers and allow dence indicates that nanoparticles (NPs) can lead to the cell migration. Moreover, by hydrolyzing extracellularly deregulation of MMP expression and/or activity both in released proteins, MMPs can change the activity of many vitro and in vivo. In this work, we summarized the current signal peptides, such as growth factors, cytokines, and state of knowledge on the impact of NPs on MMPs. The chemokines. MMPs are involved in many physiological literature analysis showed that the impact of NPs on MMP processes, such as embryogenesis, reproduction cycle, or expression and/or activity is inconclusive. NPs exhibit wound healing; however, their increased activity is also both stimulating and inhibitory effects, which might be associated with a number of pathological conditions, such dependent on multiple factors, such as NP size and coat- as diabetes, cardiovascular diseases and neurodegenera- ing or a cellular model used in the research.
    [Show full text]
  • NIH Public Access Author Manuscript Crit Rev Eukaryot Gene Expr
    NIH Public Access Author Manuscript Crit Rev Eukaryot Gene Expr. Author manuscript; available in PMC 2010 July 19. NIH-PA Author ManuscriptPublished NIH-PA Author Manuscript in final edited NIH-PA Author Manuscript form as: Crit Rev Eukaryot Gene Expr. 2008 ; 18(3): 251±278. Matrix Metalloproteinase Control of Capillary Morphogenesis Cyrus M Ghajar1, Steven C George1,2, and Andrew J Putnam1,2,3,† 1Department of Biomedical Engineering, University of California, Irvine; Irvine, CA 92697 2Department of Chemical Engineering and Materials Science, University of California, Irvine; Irvine, CA 92697 3Chao Family Comprehensive Cancer Center, University of California, Irvine; Irvine, CA 92697 Abstract Matrix metalloproteinases (MMPs) play crucial roles in a variety of normal (e.g. blood vessel formation, bone development) and pathophysiological (e.g. wound healing, cancer) processes. This is not only due to their ability to degrade the surrounding extracellular matrix (ECM), but also because MMPs function to reveal cryptic matrix binding sites, release matrix-bound growth factors inherent to these processes, and activate a variety of cell surface molecules. The process of blood vessel formation, in particular, is regulated by what is widely classified as the angiogenic switch: a mixture of both pro- and anti-angiogenic factors that function to counteract each other unless the stimuli from one side exceeds the other to disrupt the quiescent state. While it was initially thought that MMPs were strictly pro-angiogenic, new functions for this proteolytic family such as mediating vascular regression and generating matrix fragments with antiangiogenic capacities have been discovered in the last decade. These findings cast MMPs as multi-faceted pro- and anti-angiogenic effectors.
    [Show full text]
  • In Vitro Study of the Effect of Nifedipine on Human Fibroblasts
    applied sciences Article Biology of Drug-Induced Gingival Hyperplasia: In Vitro Study of the Effect of Nifedipine on Human Fibroblasts Dorina Lauritano 1,*,† , Giulia Moreo 1,†, Fedora Della Vella 2 , Annalisa Palmieri 3, Francesco Carinci 4 and Massimo Petruzzi 2 1 Centre of Neuroscience of Milan, Department of Medicine and Surgery, University of Milano-Bicocca, 20126 Milan, Italy; [email protected] 2 Interdisciplinary Department of Medicine, University of Bari, 70121 Bari, Italy; [email protected] (F.D.V.); [email protected] (M.P.) 3 Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Via Belmoro 8, 40126 Bologna, Italy; [email protected] 4 Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy; [email protected] * Correspondence: [email protected] † These authors contribute equally to this work. Abstract: Background: It has been proven that the antihypertensive agent nifedipine can cause gingi- val overgrowth as a side effect. The aim of this study was to analyze the effects of pharmacological treatment with nifedipine on human gingival fibroblasts activity, investigating the possible patho- genetic mechanisms that lead to the onset of gingival enlargement. Methods: The expression profile of 57 genes belonging to the “Extracellular Matrix and Adhesion Molecules” pathway, fibroblasts’ viability at different drug concentrations, and E-cadherin levels in treated fibroblasts were assessed using real-time Polymerase Chain Reaction, PrestoBlue™ cell viability test, and an enzyme-linked immunoassay (ELISA), respectively. Results: Metalloproteinase 24 and 8 (MMP24, MMP8) showed Citation: Lauritano, D.; Moreo, G.; significant upregulation in treated cells with respect to the control group, and cell adhesion gene Vella, F.D.; Palmieri, A.; Carinci, F.; CDH1 (E-cadherin) levels were recorded as increased in treated fibroblasts using both real-time Petruzzi, M.
    [Show full text]
  • Supplementary Table 1 Genes Tested in Qrt-PCR in Nfpas
    Supplementary Table 1 Genes tested in qRT-PCR in NFPAs Gene Bank accession Gene Description number ABI assay ID a disintegrin-like and metalloprotease with thrombospondin type 1 motif 7 ADAMTS7 NM_014272.3 Hs00276223_m1 Rho guanine nucleotide exchange factor (GEF) 3 ARHGEF3 NM_019555.1 Hs00219609_m1 BCL2-associated X protein BAX NM_004324 House design Bcl-2 binding component 3 BBC3 NM_014417.2 Hs00248075_m1 B-cell CLL/lymphoma 2 BCL2 NM_000633 House design Bone morphogenetic protein 7 BMP7 NM_001719.1 Hs00233476_m1 CCAAT/enhancer binding protein (C/EBP), alpha CEBPA NM_004364.2 Hs00269972_s1 coxsackie virus and adenovirus receptor CXADR NM_001338.3 Hs00154661_m1 Homo sapiens Dicer1, Dcr-1 homolog (Drosophila) (DICER1) DICER1 NM_177438.1 Hs00229023_m1 Homo sapiens dystonin DST NM_015548.2 Hs00156137_m1 fms-related tyrosine kinase 3 FLT3 NM_004119.1 Hs00174690_m1 glutamate receptor, ionotropic, N-methyl D-aspartate 1 GRIN1 NM_000832.4 Hs00609557_m1 high-mobility group box 1 HMGB1 NM_002128.3 Hs01923466_g1 heterogeneous nuclear ribonucleoprotein U HNRPU NM_004501.3 Hs00244919_m1 insulin-like growth factor binding protein 5 IGFBP5 NM_000599.2 Hs00181213_m1 latent transforming growth factor beta binding protein 4 LTBP4 NM_001042544.1 Hs00186025_m1 microtubule-associated protein 1 light chain 3 beta MAP1LC3B NM_022818.3 Hs00797944_s1 matrix metallopeptidase 17 MMP17 NM_016155.4 Hs01108847_m1 myosin VA MYO5A NM_000259.1 Hs00165309_m1 Homo sapiens nuclear factor (erythroid-derived 2)-like 1 NFE2L1 NM_003204.1 Hs00231457_m1 oxoglutarate (alpha-ketoglutarate)
    [Show full text]