Endothelial Notch1 signaling drives adipose tissue remodelling through regulation of vitamin A metabolism:
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| 100 | 1 | |a Taylor, Jacqueline |d 1990- |e Verfasser |0 (DE-588)1207935603 |4 aut | |
| 245 | 1 | 0 | |a Endothelial Notch1 signaling drives adipose tissue remodelling through regulation of vitamin A metabolism |c presented by Jacqueline Anne Taylor, M.Sc. |
| 264 | 1 | |a Heidelberg |c [2020] | |
| 300 | |a V, 149 Seiten |b Illustrationen, Diagramme |c 30 cm | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 502 | |b Dissertation |c Ruperto Carola University Heidelberg, Germany |d 2020 | ||
| 655 | 7 | |0 (DE-588)4113937-9 |a Hochschulschrift |2 gnd-content | |
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| _version_ | 1804182380100976640 |
|---|---|
| adam_text | TABLE
OF
CONTENTS
LIST
OF
ABBREVIATIONS
..............................................................................................................
3
LIST
OF
FIGURES
..............................................................................................................................
6
1.
INTRODUCTION
........................................................................................................................
9
1.1
THE
VASCULAR
SYSTEM
.............................................................................................................
9
1.1.1
BLOOD
VESSEL
ARCHITECTURE
.............................................................................................
9
1.1.2
ECS:
ACTIVE
GATEKEEPERS
AND
FIRST
RESPONDERS
AT
THE
BLOOD-TISSUE
INTERFACE
..........
10
1.1.3
THE
ROLE
OF
ENDOTHELIAL
CELLS
IN
IMMUNE
REGULATION
..................................................
12
1.1.4
ENDOTHELIAL
CELL
METABOLISM
DURING
ANGIOGENESIS
AND
QUIESCENCE..........................
14
1.1.5
ENDOTHELIAL
CELLS
DURING
DISEASE
.................................................................................
19
1.2
ADIPOSE
TISSUE
......................................................................................................................
20
1.2.1
ADIPOSE
TISSUE
HETEROGENEITY......................................................................................
20
1.2.2
ADIPOSE
TISSUE
INFLAMMATION
......................................................................................
24
1.2.3
THE
ADIPOSE
TISSUE
VASCULATURE
..................................................................................
26
1.2.4
COMPARING
ADIPOSE
TISSUE
IN
HUMAN
TO
MOUSE
DEPOTS
.............................................
28
1.2.5
ADIPOSE TISSUE
WASTING
................................................................................................
29
1.3
VITAMIN
A
............................................................................................................................
33
1.3.1
VITAMIN
A
METABOLISM
...............................................................................................
33
1.3.2
ADIPOSE
TISSUE
VITAMIN
A
METABOLISM
IN
OBESITY
......................................................
35
1.3.3
VITAMIN
A
METABOLISM
IN
CANCER
...............................................................................
37
1.4
THE
NOTCH
SIGNALING
PATHWAY
............................................................................................
38
1.4.1
NOTCH
SIGNALING
IN
ENDOTHELIAL
CELLS
...........................................................................
39
1.4.2
NOTCH
SIGNALING
IN
ADIPOSE
TISSUE
...............................................................................
39
1.5
AIM
OF
THE
STUDY
..................................................................................................................
41
2.
RESULTS
....................................................................................................................................
43
2.1
OVERACTIVATION
OF
ENDOTHELIAL
NOTCHL
SIGNALING
................................................................
43
2.1.1
OVERACTIVE
NOTCHL
SIGNALING
IN
THE
ENDOTHELIUM
INDUCES
LIPODYSTROPHY...............
43
2.1.2
NICD
IOE-EC
MICE
EXHIBIT
SEX-SPECIFIC
DIFFERENCES......................................................
49
2.1.3
NOTCHL
DOES
NOT
ALTER
VESSEL
DENSITY
BUT
MODIFIES
THE
BASAL
MEMBRANE
................
51
2.1.4
ENDOTHELIAL
NOTCHL
SIGNALING
INDUCES
ADIPOSE
TISSUE
FIBROSIS
.................................
54
2.1.5
ENDOTHELIAL
NOTCHL
SIGNALING
INDUCES
ADIPOSE
TISSUE
APOPTOSIS
..............................
56
2.1.6
ENDOTHELIAL
NOTCHL
SIGNALING
ALTERS
THERMOGENESIS
.................................................
58
2.1.7
NOTCHL
IN
THE
HUMAN
ADIPOSE
TISSUE
ENDOTHELIUM
REGULATES
VITAMIN
A
.................
60
2.1.8
NOTCHL
SIGNALING
REGULATES
RETINOIC
ACID
PRODUCTION
BY
ALDH1
...........................
63
1
2.1.9
ENDOTHELIAL
NOTCHL
RECRUITS
AND
REGULATES
ALDHLAL
IN
MACROPHAGES
....................
65
2.1.10
RETINOIC
ACID
REGULATES
IGFBP-3-INDUCED
FIBROSIS
AND
APOPTOSIS
..........................
71
2.1.11
NOTCHL
SIGNALING
IS
INCREASED
IN
THE
OBESE
ADIPOSE
TISSUE
ENDOTHELIUM
.................
75
2.1.12
NOTCHL
SIGNALING
IS
OVERACTIVE
IN
CACHECTIC
ADIPOSE
TISSUE
ECS
..............................
77
2.2
LOSS
OF
ENDOTHELIAL
NOTCH
SIGNALING
...................................................................................
80
2.2.1
SYSTEMIC
METABOLISM
IS
ALTERED
IN
RBPJ
K
AEC
MALE
AND
FEMALE
MICE
....................
80
2.2.2
RBPJ
K
I
AEC
MICE
EXHIBIT
SEX-SPECIFIC
ALTERATIONS
IN
ADIPOCYTE
MORPHOLOGY
...........
80
2.2.3
RBPJK
IAEC
MICE
DISPLAY INCREASED
VASCULAR
DENSITY
IN
ADIPOSE
TISSUE
.....................
83
2.2.4
INJECTION
OF
AN
ANTI-D114
ANTIBODY
MIMICS
RBPJK
IAEC
MOUSE
..................................
84
3.
DISCUSSION
..............................................................................................................................
85
3.1
RELEVANCE
OF
NOTCHL
SIGNALING
DURING
OBESITY
..................................................................
85
3.2
RELEVANCE
OF
NOTCHL
SIGNALING
DURING
CANCER
CACHEXIA
...................................................
87
3.3
CONTRIBUTION
OF
VITAMIN
A
METABOLISM
TO
DISEASE
...........................................................
88
3.4
LINK
BETWEEN
VITAMIN
A
METABOLISM
AND
IMMUNITY
.......................................................
91
3.5
RELEVANCE
OF
LOSS
OF
RBPJK
TO
VITAMIN
A
METABOLISM
......................................................
92
3.6
CONTRIBUTION
OF
THE
VASCULAR
PHENOTYPE
...........................................................................
93
3.7
STUDY
LIMITATIONS
.................................................................................................................
94
3.8
CONCLUSION
AND
OUTLOOK
.....................................................................................................
96
4.
MATERIALS
AND
METHODS
...............................................................................................
99
4.1
MATERIALS
..............................................................................................................................
99
4.1.1
ANTIBODIES
....................................................................................................................
99
4.1.2
KITS
AND
REAGENTS
......................................................................................................
101
4.1.3
BUFFERS
AND
SOLUTIONS
................................................................................................
104
4.1.4
MOUSE
STRAINS
AND
SPECIAL
DIETS
................................................................................
105
4.1.5
CELL
LINES
AND
PRIMARY
CELLS
......................................................................................
106
4.1.6
CONSUMABLES
AND
EQUIPMENT
...................................................................................
106
4.2
METHODS
..............................................................................................................................
109
4.2.1
CELL
CULTURE
..................................................................................................................
109
4.2.1
MOLECULAR
BIOLOGY
TECHNIQUES
...................................................................................
ILL
4.2.3
BIOCHEMICAL
TECHNIQUES
............................................................................................
116
4.2.4
ANIMAL
EXPERIMENTS
..................................................................................................
117
4.2.5
BIOINFORMATIC
ANALYSES
.............................................................................................
125
4.2.6
STATISTICAL
ANALYSES
....................................................................................................
126
5.
REFERENCES
.........................................................................................................................
127
6.
PUBLICATIONS
......................................................................................................................
149
2
|
| adam_txt |
TABLE
OF
CONTENTS
LIST
OF
ABBREVIATIONS
.
3
LIST
OF
FIGURES
.
6
1.
INTRODUCTION
.
9
1.1
THE
VASCULAR
SYSTEM
.
9
1.1.1
BLOOD
VESSEL
ARCHITECTURE
.
9
1.1.2
ECS:
ACTIVE
GATEKEEPERS
AND
FIRST
RESPONDERS
AT
THE
BLOOD-TISSUE
INTERFACE
.
10
1.1.3
THE
ROLE
OF
ENDOTHELIAL
CELLS
IN
IMMUNE
REGULATION
.
12
1.1.4
ENDOTHELIAL
CELL
METABOLISM
DURING
ANGIOGENESIS
AND
QUIESCENCE.
14
1.1.5
ENDOTHELIAL
CELLS
DURING
DISEASE
.
19
1.2
ADIPOSE
TISSUE
.
20
1.2.1
ADIPOSE
TISSUE
HETEROGENEITY.
20
1.2.2
ADIPOSE
TISSUE
INFLAMMATION
.
24
1.2.3
THE
ADIPOSE
TISSUE
VASCULATURE
.
26
1.2.4
COMPARING
ADIPOSE
TISSUE
IN
HUMAN
TO
MOUSE
DEPOTS
.
28
1.2.5
ADIPOSE TISSUE
WASTING
.
29
1.3
VITAMIN
A
.
33
1.3.1
VITAMIN
A
METABOLISM
.
33
1.3.2
ADIPOSE
TISSUE
VITAMIN
A
METABOLISM
IN
OBESITY
.
35
1.3.3
VITAMIN
A
METABOLISM
IN
CANCER
.
37
1.4
THE
NOTCH
SIGNALING
PATHWAY
.
38
1.4.1
NOTCH
SIGNALING
IN
ENDOTHELIAL
CELLS
.
39
1.4.2
NOTCH
SIGNALING
IN
ADIPOSE
TISSUE
.
39
1.5
AIM
OF
THE
STUDY
.
41
2.
RESULTS
.
43
2.1
OVERACTIVATION
OF
ENDOTHELIAL
NOTCHL
SIGNALING
.
43
2.1.1
OVERACTIVE
NOTCHL
SIGNALING
IN
THE
ENDOTHELIUM
INDUCES
LIPODYSTROPHY.
43
2.1.2
NICD
IOE-EC
MICE
EXHIBIT
SEX-SPECIFIC
DIFFERENCES.
49
2.1.3
NOTCHL
DOES
NOT
ALTER
VESSEL
DENSITY
BUT
MODIFIES
THE
BASAL
MEMBRANE
.
51
2.1.4
ENDOTHELIAL
NOTCHL
SIGNALING
INDUCES
ADIPOSE
TISSUE
FIBROSIS
.
54
2.1.5
ENDOTHELIAL
NOTCHL
SIGNALING
INDUCES
ADIPOSE
TISSUE
APOPTOSIS
.
56
2.1.6
ENDOTHELIAL
NOTCHL
SIGNALING
ALTERS
THERMOGENESIS
.
58
2.1.7
NOTCHL
IN
THE
HUMAN
ADIPOSE
TISSUE
ENDOTHELIUM
REGULATES
VITAMIN
A
.
60
2.1.8
NOTCHL
SIGNALING
REGULATES
RETINOIC
ACID
PRODUCTION
BY
ALDH1
.
63
1
2.1.9
ENDOTHELIAL
NOTCHL
RECRUITS
AND
REGULATES
ALDHLAL
IN
MACROPHAGES
.
65
2.1.10
RETINOIC
ACID
REGULATES
IGFBP-3-INDUCED
FIBROSIS
AND
APOPTOSIS
.
71
2.1.11
NOTCHL
SIGNALING
IS
INCREASED
IN
THE
OBESE
ADIPOSE
TISSUE
ENDOTHELIUM
.
75
2.1.12
NOTCHL
SIGNALING
IS
OVERACTIVE
IN
CACHECTIC
ADIPOSE
TISSUE
ECS
.
77
2.2
LOSS
OF
ENDOTHELIAL
NOTCH
SIGNALING
.
80
2.2.1
SYSTEMIC
METABOLISM
IS
ALTERED
IN
RBPJ
K
'
AEC
MALE
AND
FEMALE
MICE
.
80
2.2.2
RBPJ
K
I
AEC
MICE
EXHIBIT
SEX-SPECIFIC
ALTERATIONS
IN
ADIPOCYTE
MORPHOLOGY
.
80
2.2.3
RBPJK
IAEC
MICE
DISPLAY INCREASED
VASCULAR
DENSITY
IN
ADIPOSE
TISSUE
.
83
2.2.4
INJECTION
OF
AN
ANTI-D114
ANTIBODY
MIMICS
RBPJK
IAEC
MOUSE
.
84
3.
DISCUSSION
.
85
3.1
RELEVANCE
OF
NOTCHL
SIGNALING
DURING
OBESITY
.
85
3.2
RELEVANCE
OF
NOTCHL
SIGNALING
DURING
CANCER
CACHEXIA
.
87
3.3
CONTRIBUTION
OF
VITAMIN
A
METABOLISM
TO
DISEASE
.
88
3.4
LINK
BETWEEN
VITAMIN
A
METABOLISM
AND
IMMUNITY
.
91
3.5
RELEVANCE
OF
LOSS
OF
RBPJK
TO
VITAMIN
A
METABOLISM
.
92
3.6
CONTRIBUTION
OF
THE
VASCULAR
PHENOTYPE
.
93
3.7
STUDY
LIMITATIONS
.
94
3.8
CONCLUSION
AND
OUTLOOK
.
96
4.
MATERIALS
AND
METHODS
.
99
4.1
MATERIALS
.
99
4.1.1
ANTIBODIES
.
99
4.1.2
KITS
AND
REAGENTS
.
101
4.1.3
BUFFERS
AND
SOLUTIONS
.
104
4.1.4
MOUSE
STRAINS
AND
SPECIAL
DIETS
.
105
4.1.5
CELL
LINES
AND
PRIMARY
CELLS
.
106
4.1.6
CONSUMABLES
AND
EQUIPMENT
.
106
4.2
METHODS
.
109
4.2.1
CELL
CULTURE
.
109
4.2.1
MOLECULAR
BIOLOGY
TECHNIQUES
.
ILL
4.2.3
BIOCHEMICAL
TECHNIQUES
.
116
4.2.4
ANIMAL
EXPERIMENTS
.
117
4.2.5
BIOINFORMATIC
ANALYSES
.
125
4.2.6
STATISTICAL
ANALYSES
.
126
5.
REFERENCES
.
127
6.
PUBLICATIONS
.
149
2 |
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| any_adam_object_boolean | 1 |
| author | Taylor, Jacqueline 1990- |
| author_GND | (DE-588)1207935603 |
| author_facet | Taylor, Jacqueline 1990- |
| author_role | aut |
| author_sort | Taylor, Jacqueline 1990- |
| author_variant | j t jt |
| building | Verbundindex |
| bvnumber | BV047242105 |
| ctrlnum | (OCoLC)1245373931 (DE-599)DNB1226949398 |
| discipline | Biologie |
| discipline_str_mv | Biologie |
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| illustrated | Illustrated |
| index_date | 2024-07-03T17:04:46Z |
| indexdate | 2024-07-10T09:06:37Z |
| institution | BVB |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-032646350 |
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| owner_facet | DE-355 DE-BY-UBR |
| physical | V, 149 Seiten Illustrationen, Diagramme 30 cm |
| publishDate | 2020 |
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| spelling | Taylor, Jacqueline 1990- Verfasser (DE-588)1207935603 aut Endothelial Notch1 signaling drives adipose tissue remodelling through regulation of vitamin A metabolism presented by Jacqueline Anne Taylor, M.Sc. Heidelberg [2020] V, 149 Seiten Illustrationen, Diagramme 30 cm txt rdacontent n rdamedia nc rdacarrier Dissertation Ruperto Carola University Heidelberg, Germany 2020 (DE-588)4113937-9 Hochschulschrift gnd-content B:DE-101 application/pdf https://d-nb.info/1226949398/04 Inhaltsverzeichnis DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=032646350&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Taylor, Jacqueline 1990- Endothelial Notch1 signaling drives adipose tissue remodelling through regulation of vitamin A metabolism |
| subject_GND | (DE-588)4113937-9 |
| title | Endothelial Notch1 signaling drives adipose tissue remodelling through regulation of vitamin A metabolism |
| title_auth | Endothelial Notch1 signaling drives adipose tissue remodelling through regulation of vitamin A metabolism |
| title_exact_search | Endothelial Notch1 signaling drives adipose tissue remodelling through regulation of vitamin A metabolism |
| title_exact_search_txtP | Endothelial Notch1 signaling drives adipose tissue remodelling through regulation of vitamin A metabolism |
| title_full | Endothelial Notch1 signaling drives adipose tissue remodelling through regulation of vitamin A metabolism presented by Jacqueline Anne Taylor, M.Sc. |
| title_fullStr | Endothelial Notch1 signaling drives adipose tissue remodelling through regulation of vitamin A metabolism presented by Jacqueline Anne Taylor, M.Sc. |
| title_full_unstemmed | Endothelial Notch1 signaling drives adipose tissue remodelling through regulation of vitamin A metabolism presented by Jacqueline Anne Taylor, M.Sc. |
| title_short | Endothelial Notch1 signaling drives adipose tissue remodelling through regulation of vitamin A metabolism |
| title_sort | endothelial notch1 signaling drives adipose tissue remodelling through regulation of vitamin a metabolism |
| topic_facet | Hochschulschrift |
| url | https://d-nb.info/1226949398/04 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=032646350&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT taylorjacqueline endothelialnotch1signalingdrivesadiposetissueremodellingthroughregulationofvitaminametabolism |
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