Publications
Detailed Information
Hyperglycemia-induced Jagged 1 overexpression in endothelial cells causes retinal capillary regression in a murine model of diabetes mellitus : 혈관내피세포에서 고농도 당에 의한 Jagged1 발현 증가와 당뇨병성 혈관병증의 병인기전에 관한 연구
DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | 김효수 | - |
dc.contributor.author | 최영은 | - |
dc.date.accessioned | 2017-07-14T01:46:26Z | - |
dc.date.available | 2017-07-14T01:46:26Z | - |
dc.date.issued | 2016-08 | - |
dc.identifier.other | 000000137046 | - |
dc.identifier.uri | https://hdl.handle.net/10371/122331 | - |
dc.description | 학위논문 (박사)-- 서울대학교 대학원 : 의과학과, 2016. 8. 김효수. | - |
dc.description.abstract | Introduction: Regulation of vascular morphogenesis (sprouting, branching, lumenization, regression) by Notch signaling has been well characterized during vascular development. In adult mature vasculature, resting endothelial cells (ECs) also retain their growth potential that is activated under certain circumstances, but less is known about the maintenance mechanism of endothelial homeostasis.
Methods: We developed an in vitro model of human angiogenesis. Human ECs and smooth muscle cells (SMCs) in spheroid were co-cultivated on SMC monolayer under high glucose or control conditions. For in vivo loss-of-function studies, we used both EC-specific Jagged1 (Jag1) heterozygous deficient mice (Tie2-Cre+ | - |
dc.description.abstract | Jag1flox/+) and ECs-specific inducible Jag1 deficient mice (Tie2-CreERT2+ | - |
dc.description.abstract | Jag1flox/flox).
Results: Using the in vitro angiogenesis model, we observed high glucose-induced abnormal angiogenesis characterized by increased sprouting and branching points, decreased vascular diameter and length, and destabilization of the tubes. As the underlying mechanism, we identified the PKC- and NF-κB-dependent upregulation of Jag1 in ECs under high glucose condition. Increased expression of Jag1 was also observed in retinal ECs of streptozotocin-induced diabetic model. We confirmed attenuation of hyperglycemia-induced retinal vascular abnormalities in EC-specific Jag1 deletion mice. Conclusions: We found that increased expression of Jag1 might be a mechanism of diabetic microvasculopathy. Correction of the pathologic angiogenesis by modulating the aberrant signaling in the present study highlighted a future direction of treatment of diabetic vasculopathy other than glucose control. | - |
dc.description.tableofcontents | General Introduction 1
Chapter 1 High glucose-induced Jagged1 in endothelial cells disturbs Notch signaling for angiogenesis: A novel mechanism of diabetic vasculopathy 3 Introduction 4 Material and Methods 7 Results 15 Discussion 39 Chapter 2 Hyperglycemia-induced Jagged1 overexpression in endothelial cells causes retinal capillary regression in a murine model of diabetes mellitus: Insights into diabetic retinopathy 49 Introduction 50 Material and Methods 53 Results 63 Discussion 94 References 106 Abstract in Korean 110 | - |
dc.format | application/pdf | - |
dc.format.extent | 7036954 bytes | - |
dc.format.medium | application/pdf | - |
dc.language.iso | en | - |
dc.publisher | 서울대학교 대학원 | - |
dc.subject | Diabetes mellitus | - |
dc.subject | microvasculopathy | - |
dc.subject | Notch signaling | - |
dc.subject.ddc | 610 | - |
dc.title | Hyperglycemia-induced Jagged 1 overexpression in endothelial cells causes retinal capillary regression in a murine model of diabetes mellitus | - |
dc.title.alternative | 혈관내피세포에서 고농도 당에 의한 Jagged1 발현 증가와 당뇨병성 혈관병증의 병인기전에 관한 연구 | - |
dc.type | Thesis | - |
dc.description.degree | Doctor | - |
dc.citation.pages | vii, 111 | - |
dc.contributor.affiliation | 의과대학 의과학과 | - |
dc.date.awarded | 2016-08 | - |
- Appears in Collections:
- Files in This Item:
Item View & Download Count
Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.