The role of Lasp1 in inflammatory synovial joint destruction: = Die Rolle von Lasp1 in der inflammatorischen Gelenkdestruktion
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| 1. Verfasser: | |
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| Format: | Abschlussarbeit Buch |
| Sprache: | English |
| Veröffentlicht: |
[Münster]
2018
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| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis Inhaltsverzeichnis |
| Beschreibung: | XII, 90 Blätter Illustrationen 30 cm |
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MARC
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| 245 | 1 | 0 | |a The role of Lasp1 in inflammatory synovial joint destruction |b = Die Rolle von Lasp1 in der inflammatorischen Gelenkdestruktion |c vorgelegt von Denise Beckmann |
| 246 | 1 | 3 | |a Die Rolle von Lasp1 in der inflammatorischen Gelenkdestruktion |
| 246 | 1 | 1 | |a Die Rolle von Lasp1 in der inflammatorischen Gelenkdestruktion |
| 264 | 1 | |a [Münster] |c 2018 | |
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Datensatz im Suchindex
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| adam_text | CONTENTS
1 INTRODUCTION 1
1.1 CHARACTERISTICS OF RHEUMATOID ARTHRITIS (RA) 1
1.2 PATHOPHYSIOLOGY OF RA 2
1.3 THE ROLE OF RA-FLS IN RA 3
1.4 RA MOUSE MODELS 4
1.4.1 THE HUMAN TNFALPHA TRANSGENIC MOUSE MODEL 5
1.4.2 THE G6PI MOUSE MODEL 5
1.5 EPITHELIAL CELL JUNCTIONS 6
1.6 THE ACTIN-RELATED PROTEIN (ARP2/3) COMPLEX 8
1.7 THE LIM-AND-SH3-DOMAIN-PROTEIN 1 (LASPI) 10
1.8 AIMS OF THIS THESIS 13
2 MATERIALS AND METHODS 14
2.1 MATERIALS 14
2.1.1 REAGENTS 14
2.1.2 LABORATORY CONSUMABLES 14
2.1.3 CELL CULTURE MATERIAL 15
2.1.4 MATERIAL FOR BIOCHEMICAL ASSAYS 15
2.1.5 KITS 16
2.1.6 EQUIPMENT AND SOFTWARE 16
2.1.7 BUFFERS AND SOLUTIONS 17
2.1.8 ANTIBODIES 18
2.1.9 PRIMERS FOR MOUSE GENOTYPING 19
2.2 ANIMAL EXPERIMENTAL METHODS 20
2.2.1 HTNFTG MOUSE MODEL 20
2.2.2 G6PI-INDUCED ARTHRITIS MODEL 20
2.3 CELL CULTURE METHODS 21
2.3.1 ISOLATION OF HUMAN SYNOVIAL TISSUE AND HUMAN FLS 21
2.3.2 ISOLATION OF MURINE FLS 22
2.3.3 ISOLATION OF MURINE MEFS 22
2.3.4 PASSAGING CELLS 22
2.3.5 ISOLATION OF MURINE BMM 22
2.3.6 SYNOVIAL ORGAN CULTURES 22
2.3.7 CELL MOTILITY ASSAYS 23
2.3.8 CYQUANT CELL PROLIFERATION ASSAY 23
2.3.9 ANALYSIS OF THE ACTIN CYTOSKELETON OF FLS BY EM 23
2.3.10 ELECTRIC CELL/SUBSTRATE IMPEDANCE SENSING ASSAY 23
2.3.11 LENTIVIRAL GENE TRANSFER AND LIVE-CELL IMAGING 24
2.3.12 TRANSFECTION OF LASPI_/ MEFS 24
2.3.13 CO-LMMUNOPRECIPITATION (CO-IP) 25
2.3.14 STIMULATION EXPERIMENTS 25
2.4 HISTOLOGICAL METHODS 25
2.4.1 IMMUNOHISTOCHEMISTRY 26
2.4.2 H&E STAINING OF PARAFFIN SECTIONS 26
2.4.3 TOLUIDINE-BLUE STAINING OF PARAFFIN SECTIONS 26
2.4.4 IMMUNOFLUORESCENCE STAININGS OF FLS 27
2.4.5 TRAP STAINING 27
2.4.6 HISTOMORPHOMETRIC ANALYSIS 27
2.5 MICRO-COMPUTED TOMOGRAPHIC ANALYSIS (PCT) 28
2.6 MOLECULAR BIOLOGICAL METHODS 28
2.6.1 GENOMIC DNA PREPARATION FROM MOUSE TISSUES 28
2.6.2 MOUSE GENOTYPING 28
2.6.3 AGAROSE GEL ELECTROPHORESIS 29
2.7 PROTEIN BIOCHEMICAL METHODS 29
2.7.1 CELL LYSIS 29
2.7.2 QUANTITATIVE DETERMINATION OF PROTEIN CONCENTRATION 30
2.7.3 SOS-PAGE AND WESTERN BLOTTING 30
2.7.4 STRIPPING OF PVDF-MEMBRANES 31
2.8 STATISTIC ANALYSIS 31
2.9 DATA ANALYSIS 31
3 RESULTS 32
3.1 LASPI EXPRESSION IN RHEUMATOID ARTHRITIS 32
3.1.1 LASPI EXPRESSION WAS UPREGULATED IN HUMAN RHEUMATOID
ARTHRITIS AND IN ANIMAL MODELS OF THE DISEASE 32
3.2 FUNCTIONAL ASPECTS OF LASPI DURING ARTHRITIS 34
3.3 EFFECTS OF LASPI DELETION ON FORMATION OF ADHERENS JUNCTIONS 39
3.3.1 EXPRESSION OF ADHERENS JUNCTION PROTEINS IN FLS 39
3.3.2 IDENTIFICATION OF LASPI INTERACTION PARTNERS WITHIN
THE AJ COMPLEX 41
3.3.3 IDENTIFICATION OF ARP2/3 AS A LASPI INTERACTION PARTNER
WITHIN THE CADHERIN-11 ADHESION COMPLEX 45
3.4 EFFECTS OF LASPI DELETION ON IL-1K AND PDGF SIGNALLING 47
3.4.1 EFFECTS OF LASPI DELETION ON IL-1U SIGNALLING 47
3.4.2 EFFECTS OF LASPI DELETION ON PDGF SIGNALLING 49
3.5 EFFECTS OF LASPI DEFICIENCY IN THE HTNFTG MOUSE MODEL 50
3.6 BLOCKING OF LASPI FUNCTION BY INHIBITORY PEPTIDES IN FLS 54
4 DISCUSSION 57
4.1 LASPI EXPRESSION IS UPREGULATED IN SYNOVIAL TISSUE AND
ISOLATED FLS FROM RA PATIENTS AND ARTHRITIC MICE 57
4.2 THE DELETION OF LASPI DURING RA LEADS TO A REDUCTION
IN THE MIGRATION RATE OF FLS 58
4.3 LASPI IS A KEY COMPONENT OF THE ADHERENS JUNCTION
MACHINERY IN FLS 60
4.4 THE DELETION OF LASPI DURING RA LEADS TO A DIMINISHED
INVASIVE CAPACITY OF FLS 62
4.5 LASPI DEFICIENCY INHIBITS CLINICAL SIGNS OF ARTHRITIS IN THE
HTNFTG MOUSE MODEL 64
5 CONCLUSIONS AND OUTLOOK 67
BIBLIOGRAPHY 69
LEBENSLAUF 82
PUBLIKATIONEN 84
VEROEFFENTLICHE ABSTRACTS 85
VORTRAEGE 88
DANKSAGUNG 89
EIDESSTATTLICHE ERKLAERUNG 90
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| any_adam_object | 1 |
| author | Beckmann, Denise 1982- |
| author_GND | (DE-588)1170190227 |
| author_facet | Beckmann, Denise 1982- |
| author_role | aut |
| author_sort | Beckmann, Denise 1982- |
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| building | Verbundindex |
| bvnumber | BV045354558 |
| ctrlnum | (OCoLC)1136437308 (DE-599)DNB1169170463 |
| discipline | Medizin |
| format | Thesis Book |
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| indexdate | 2024-07-10T08:15:48Z |
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| language | English |
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| spelling | Beckmann, Denise 1982- Verfasser (DE-588)1170190227 aut The role of Lasp1 in inflammatory synovial joint destruction = Die Rolle von Lasp1 in der inflammatorischen Gelenkdestruktion vorgelegt von Denise Beckmann Die Rolle von Lasp1 in der inflammatorischen Gelenkdestruktion [Münster] 2018 XII, 90 Blätter Illustrationen 30 cm txt rdacontent n rdamedia nc rdacarrier Dissertation Westfälische Wilhelms-Universität Münster 2018 Beschränkt für den Austausch (DE-588)4113937-9 Hochschulschrift gnd-content B:DE-101 application/pdf http://d-nb.info/1169170463/04 Inhaltsverzeichnis DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=030741162&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Beckmann, Denise 1982- The role of Lasp1 in inflammatory synovial joint destruction = Die Rolle von Lasp1 in der inflammatorischen Gelenkdestruktion |
| subject_GND | (DE-588)4113937-9 |
| title | The role of Lasp1 in inflammatory synovial joint destruction = Die Rolle von Lasp1 in der inflammatorischen Gelenkdestruktion |
| title_alt | Die Rolle von Lasp1 in der inflammatorischen Gelenkdestruktion |
| title_auth | The role of Lasp1 in inflammatory synovial joint destruction = Die Rolle von Lasp1 in der inflammatorischen Gelenkdestruktion |
| title_exact_search | The role of Lasp1 in inflammatory synovial joint destruction = Die Rolle von Lasp1 in der inflammatorischen Gelenkdestruktion |
| title_full | The role of Lasp1 in inflammatory synovial joint destruction = Die Rolle von Lasp1 in der inflammatorischen Gelenkdestruktion vorgelegt von Denise Beckmann |
| title_fullStr | The role of Lasp1 in inflammatory synovial joint destruction = Die Rolle von Lasp1 in der inflammatorischen Gelenkdestruktion vorgelegt von Denise Beckmann |
| title_full_unstemmed | The role of Lasp1 in inflammatory synovial joint destruction = Die Rolle von Lasp1 in der inflammatorischen Gelenkdestruktion vorgelegt von Denise Beckmann |
| title_short | The role of Lasp1 in inflammatory synovial joint destruction |
| title_sort | the role of lasp1 in inflammatory synovial joint destruction die rolle von lasp1 in der inflammatorischen gelenkdestruktion |
| title_sub | = Die Rolle von Lasp1 in der inflammatorischen Gelenkdestruktion |
| topic_facet | Hochschulschrift |
| url | http://d-nb.info/1169170463/04 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=030741162&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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