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| Main Author: | |
|---|---|
| Format: | Thesis/Dissertation Book |
| Language: | English |
| Published: |
2013
|
| Subjects: | |
| Links: | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=026060172&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| Item Description: | Zsfassung in engl. und dt. Sprache |
| Physical Description: | XVIII, 133 S. Ill., graph. Darst. |
Staff View
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| 245 | 1 | 0 | |a Role of hepatic stellate cell-expressed Endosialin in liver health and disease |c [vorgelegt von Matthias Wieland] |
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Record in the Search Index
| DE-BY-UBR_call_number | 24/V22485 |
|---|---|
| DE-BY-UBR_katkey | 5230738 |
| DE-BY-UBR_location | UB Magazin |
| DE-BY-UBR_media_number | 069038097856 |
| _version_ | 1835111610113327104 |
| adam_text | IMAGE 1
TABLE OF CONTENT
TABLE OF CONTENT
ACKNOWLEDGEMENT - DANKSAGUNG V
LIST OF FIGURES XI
LIST OF TABLES XIII
ZUSAMMENFASSUNG XV
ABSTRACT XVII
1 INTRODUCTION 1
1.1 THE LIVER: ANATOMY AND FUNCTION 1
1.2 LIVER FIBROSIS AND CIRRHOSIS 3
1.2.1 DESCRIPTION AND ETIOLOGY OF LIVER FIBROSIS AND CIRRHOSIS 3
1.2.2 PATHOGENESIS O F LIVER FIBROSIS 4
1.2.3 ANIMAL MODELS OF LIVER FIBROGENESIS WITH EMPHASIS ON CARBON
TETRACHLORIDE 9
1.3 LIVER TUMORS 10
1.3.1 HEPATOCELLULAR CARCINOMA - EPIDEMIOLOGY AND RISK FACTORS 11
1.3.2 PATHOLOGY AND PATHOGENESIS O F HCC 12
1.3.3 TREATMENT OF HCC 14
1.4 LIVER REGENERATION 16
1.4.1 A UNIQUE PROPERTY OF A VITAL ORGAN 16
1.4.2 MOLECULAR REGULATION O F LIVER REGENERATION 18
1.5 ENDOSIALIN 23
1.5.1 IDENTIFICATION OF ENDOSIALIN 23
1.5.2 THE EXPRESSION PATTERN OF ENDOSIALIN 24
1.5.3 APPROACHES TO ANALYZE THE FUNCTION OF ENDOSIALIN 26
1.6 RATIONALE AND SCOPE OF THE PRESENT STUDY 29
2 RESULTS 31
2.1 EXPRESSION OF ENDOSIALIN IN HUMAN HEPATIC STELLATE CELLS AND PORTAL
FIBROBLASTS 31
2.2 ENDOSIALIN EXPRESSION IS UPREGULATED IN HUMAN LIVER FIBROSIS AND
CIRRHOSIS 32
2.3 THE EXPRESSION O F ENDOSIALIN INCREASES EARLY UPON DAMAGE IN HUMAN
LIVERS 33
2.4 ESTABLISHMENT O F AN IMPROVED MURINE HEPATIC STELLATE CELL ISOLATION
PROTOCOL 35
2.5 ANALYSIS OF ENDOSIALIN EXPRESSION IN MURINE LIVERS 38
VII
HTTP://D-NB.INFO/1037126297
IMAGE 2
TABLE OF CONTENT
2.6 ENDOSIALIN IS AN EARLY MARKER OF ACUTE LIVER INJURY IN MICE 39
2.7 MORPHOLOGICAL AND FUNCTIONAL ANALYSIS OF ENDOSIALIN WT AND KO MOUSE
LIVERS 4 1
2.8 FIBROSIS IN MICE LEADS TO INCREASED EXPRESSION O F ENDOSIALIN BY HSC
42
2.9 ANALYSIS OF CCI 4 -INDUCED LIVER DAMAGE IN ENDOSIALIN WT AND KO MICE
43
2.10 ENDOSIALIN DEFICIENCY IN MICE ATTENUATES LATE EXPERIMENTAL FIBROSIS
44
2.11 THE EXPRESSION OF TIMP1 IS REDUCED IN FIBROTIC LIVERS OF ENDOSIALIN
KO MICE 46
2.12 HSC MARKER EXPRESSION IS REDUCED IN FIBROTIC LIVERS OF ENDOSIALIN
KO MICE AFTER SIX WEEKS OF
CCI 4 TREATMENT 48
2.13 ANALYSIS OF KUPFFER CELLS IN ENDOSIALIN WT AND KO MICE DURING
EXPERIMENTALLY-INDUCED
FIBROSIS 49
2.14 INCREASED PROLIFERATION OF HEPATOCYTES DURING FIBROSIS IN
ENDOSIALIN KO MICE 5 1
2.15 EARLY ENHANCED PROLIFERATION OF HEPATOCYTES IN ENDOSIALIN KO MICE
AFTER 1/3 PARTIAL
HEPATECTOMY 53
2.16 ANALYSIS OF LIVER CELL PROLIFERATION IN ENDOSIALIN WT AND KO MICE
AFTER 2/3 PARTIAL
HEPATECTOMY 54
2.17 THE EXPRESSION PATTERN OF ENDOSIALIN AFTER 2/3 PARTIAL HEPATECTOMY
57
2.18 HYPOXIA IS REDUCED IN ENDOSIALIN KO MICE AFTER 2/3 PARTIAL
HEPATECTOMY 58
2.19 EXPRESSION ANALYSIS OF REGENERATION-ASSOCIATED CYTOKINES AFTER 2/3
PARTIAL HEPATECTOMY..60
2.20 MICROARRAY ANALYSIS OF ISOLATED QUIESCENT AND IN VIVO ACTIVATED
HEPATIC STELLATE CELLS OF
ENDOSIALIN WT AND KO MICE 61
2.21 EXPRESSION ANALYSIS OF SINUSOIDAL ENDOTHELIAL CELLS FROM
ENDOSIALIN-DEFICIENT AND WT MICE
AFTER PARTIAL HEPATECTOMY 65
2.22 ENDOSIALIN IS EXPRESSED IN THE STROMA OF HUMAN HEPATOCELLULAR
CARCINOMA 67
2.23 ANALYSIS OF EARLY HCC TUMOR DEVELOPMENT IN ENDOSIALIN WT AND KO AST
MICE 68
2.24 HCC TUMORIGENESIS IS ACCELERATED IN ENDOSIALIN KO AST MICE 70
2.25 ENDOSIALIN EXPRESSION INVERSELY CORRELATES WITH PROLIFERATION IN
HUMAN HCC 74
3 DISCUSSION 77
3.1 ENDOSIALIN IN LIVER HEALTH AND DISEASE 77
3.1.1 EXPRESSION OF ENDOSIALIN BY HSC IS UPREGULATED DURING LIVER
FIBROSIS IN MICE AND
HUMANS 77
3.1.2 THE FUNCTION OF ENDOSIALIN DURING LIVER FIBROSIS AND REGENERATION
78
3.1.3 ANALYSIS OF ENDOSIALIN-MEDIATED CONTROL OF HEPATOCYTE
PROLIFERATION 79
3.1.4 THE INFLUENCE OF ENDOSIALIN IN HCC PROGRESSION 81
VIII
IMAGE 3
TABLE OF CONTENT
3.2 MODEL: ENDOSIALIN-EXPRESSING HSC CONTROL THE PROLIFERATION OF
HEPATOCYTES 82
3.3 HEPATOCYTE NEIGHBORS ORCHESTRATE LIVER REGENERATION 84
3.4 CONSEQUENCES FOR ANTI-FIBROSIS THERAPY IN THE LIVER 85
4 METHODS 87
4.1 PATIENT SPECIMEN - ETHIC DECLARATION 87
4.2 ANIMALS 87
4.2.1 ANIMAL WELFARE 87
4.2.2 CCI 4 -INDUCED EXPERIMENTAL LIVER DAMAGE 88
4.2.3 PARTIAL HEPATECTOMY 88
4.2.4 ADENO-CRE INJECTION IN AST MICE 89
4.2.5 MAGNETIC RESONANCE IMAGING 89
4.2.6 COMPUTERTOMOGRAPHY 89
4.3 MURINE CELL ISOLATIONS 90
4.3.1 HEPATOCYTE ISOLATIONS 90
4.3.2 LSEC/KUPFFER CELL ISOLATIONS 90
4.3.3 HSC ISOLATIONS 91
4.4 CELL CULTURE O F LX2 HUMAN HSC 92
4.5 HISTOCHEMICAL METHODS 92
4.5.1 PREPARATION OF FORMALIN-FIXED PARAFFIN-EMBEDDED TISSUES AND
SECTIONS 92
4.5.2 PREPARATION OF CRYO BLOCKS AND SECTIONS 92
4.5.3 HE-STAINING 93
4.5.4 SIRIUS RED STAINING 93
4.5.5 IMMUNOHISTOCHEMISTRY 93
4.5.6 DOUBLE IMMUNOFLUORESCENCE STAININGS ON CRYOSECTIONS OR FIXED CELLS
94
4.6 MOLECULAR BIOLOGY METHODS 95
4.6.1 DNA ISOLATION FROM TAIL 95
4.6.2 PCR - POLYMERASE CHAIN REACTION 95
4.6.3 AGAROSE GEL ELECTROPHORESIS 96
4.6.4 RNA PREPARATION FROM CELLS 96
4.6.5 RNA PREPARATION FROM ORGANS 97
4.6.6 RNA ISOLATION FROM ISOLATED LSEC 97
IX
IMAGE 4
TABLE OF CONTENT
4.6.7 CDNA GENERATION 98
4.6.8 QUANTITATIVE REAL TIME-PCR (QRT-PCR) 99
4.6.9 MICROARRAY 100
4.7 PROTEIN CHEMICAL METHODS 100
4.7.1 PREPARATION OF PROTEIN LYSATES FROM ORGANS 100
4.7.2 PROTEIN CONCENTRATION MEASUREMENTS 100
4.7.3 WESTERN BLOT ANALYSIS 101
4.7.4 FLUORESCENCE ACTIVATED CELL SORTING-FACS 102
4.7.5 SERUM PREPARATION AND BLOOD ENZYME MEASUREMENTS 102
4.8 STATISTICAL ANALYSIS 102
5 MATERIALS 103
5.1 CHEMICALS 103
5.2 PRIMERS 103
5.3 PCR AND QRT-PCR REAGENTS 104
5.4 KITS 104
5.5 CELL CULTURE 105
5.6 CONSUMABLES 105
5.7 ANTIBODIES 105
5.7.1 PRIMARY ANTIBODIES 105
5.7.2 SECONDARY ANTIBODIES 106
5.8 ADDITIONAL STAINING REAGENTS 107
5.9 MISCELLANEOUS 107
5.10 ANASTHETICS 107
5.11 SOLUTIONS, BUFFERS, AND MEDIA 107
6 ABBREVIATIONS 113
7 REFERENCES 117
X
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| dewey-ones | 610 - Medicine and health 570 - Biology |
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| dewey-search | 610 570 |
| dewey-sort | 3610 |
| dewey-tens | 610 - Medicine and health 570 - Biology |
| discipline | Biologie Medizin |
| format | Thesis Book |
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| language | English |
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| spellingShingle | Wieland, Matthias Role of hepatic stellate cell-expressed Endosialin in liver health and disease |
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| title | Role of hepatic stellate cell-expressed Endosialin in liver health and disease |
| title_auth | Role of hepatic stellate cell-expressed Endosialin in liver health and disease |
| title_exact_search | Role of hepatic stellate cell-expressed Endosialin in liver health and disease |
| title_full | Role of hepatic stellate cell-expressed Endosialin in liver health and disease [vorgelegt von Matthias Wieland] |
| title_fullStr | Role of hepatic stellate cell-expressed Endosialin in liver health and disease [vorgelegt von Matthias Wieland] |
| title_full_unstemmed | Role of hepatic stellate cell-expressed Endosialin in liver health and disease [vorgelegt von Matthias Wieland] |
| title_short | Role of hepatic stellate cell-expressed Endosialin in liver health and disease |
| title_sort | role of hepatic stellate cell expressed endosialin in liver health and disease |
| topic_facet | Hochschulschrift |
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