Cell biology and mechanistic basis of elevated netosis in diabetes
When activated, neutrophils can unravel their chromatin and release it along with toxic granular proteins, forming neutrophil extracellular traps (NETs). Being highly pro-inflammatory, NETs are injurious to organs and tissues. In diabetes, formation of NETs (NETosis) is exacerbated, causing diabetic...
| Main Author: | |
|---|---|
| Other Authors: | |
| Format: | Thesis-Doctor of Philosophy |
| Language: | English |
| Published: |
Nanyang Technological University
2025
|
| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/182659 |
| _version_ | 1826115603614662656 |
|---|---|
| author | Wang, Liang De |
| author2 | Christine Wong Siu Ling |
| author_facet | Christine Wong Siu Ling Wang, Liang De |
| author_sort | Wang, Liang De |
| collection | NTU |
| description | When activated, neutrophils can unravel their chromatin and release it along with toxic granular proteins, forming neutrophil extracellular traps (NETs). Being highly pro-inflammatory, NETs are injurious to organs and tissues. In diabetes, formation of NETs (NETosis) is exacerbated, causing diabetic complications including diabetic retinopathy and delayed wound healing. How diabetes augments NETosis remains unclear. Herein, I report that sirtuin 1 (SIRT1) functions as an endogenous inhibitor of NETosis in healthy neutrophils. Reduction in SIRT1 activity in diabetes resulted in excessive NET formation, which could be normalized by SIRT1 activators. My work also defined the role of oxidized DNA and endoplasmic reticulum stress in the activation of neutrophil NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome in the generation of excessive NETs in diabetes. The findings have advanced our understanding of NETosis biology and laid an important foundation for the development of novel therapeutics for combating diabetic complications and beyond. |
| first_indexed | 2025-03-09T11:25:49Z |
| format | Thesis-Doctor of Philosophy |
| id | ntu-10356/182659 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2025-03-09T11:25:49Z |
| publishDate | 2025 |
| publisher | Nanyang Technological University |
| record_format | dspace |
| spelling | ntu-10356/1826592025-03-04T02:57:33Z Cell biology and mechanistic basis of elevated netosis in diabetes Wang, Liang De Christine Wong Siu Ling Lee Kong Chian School of Medicine (LKCMedicine) christine.wongsl@ntu.edu.sg Medicine, Health and Life Sciences When activated, neutrophils can unravel their chromatin and release it along with toxic granular proteins, forming neutrophil extracellular traps (NETs). Being highly pro-inflammatory, NETs are injurious to organs and tissues. In diabetes, formation of NETs (NETosis) is exacerbated, causing diabetic complications including diabetic retinopathy and delayed wound healing. How diabetes augments NETosis remains unclear. Herein, I report that sirtuin 1 (SIRT1) functions as an endogenous inhibitor of NETosis in healthy neutrophils. Reduction in SIRT1 activity in diabetes resulted in excessive NET formation, which could be normalized by SIRT1 activators. My work also defined the role of oxidized DNA and endoplasmic reticulum stress in the activation of neutrophil NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome in the generation of excessive NETs in diabetes. The findings have advanced our understanding of NETosis biology and laid an important foundation for the development of novel therapeutics for combating diabetic complications and beyond. Doctor of Philosophy 2025-02-14T10:57:06Z 2025-02-14T10:57:06Z 2024 Thesis-Doctor of Philosophy Wang, L. D. (2024). Cell biology and mechanistic basis of elevated netosis in diabetes. Doctoral thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/182659 https://hdl.handle.net/10356/182659 10.32657/10356/182659 en This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0). application/pdf Nanyang Technological University |
| spellingShingle | Medicine, Health and Life Sciences Wang, Liang De Cell biology and mechanistic basis of elevated netosis in diabetes |
| title | Cell biology and mechanistic basis of elevated netosis in diabetes |
| title_full | Cell biology and mechanistic basis of elevated netosis in diabetes |
| title_fullStr | Cell biology and mechanistic basis of elevated netosis in diabetes |
| title_full_unstemmed | Cell biology and mechanistic basis of elevated netosis in diabetes |
| title_short | Cell biology and mechanistic basis of elevated netosis in diabetes |
| title_sort | cell biology and mechanistic basis of elevated netosis in diabetes |
| topic | Medicine, Health and Life Sciences |
| url | https://hdl.handle.net/10356/182659 |
| work_keys_str_mv | AT wangliangde cellbiologyandmechanisticbasisofelevatednetosisindiabetes |